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  • Mice  (416)
  • Models, Biological  (138)
  • American Association for the Advancement of Science (AAAS)  (539)
  • 2005-2009  (454)
  • 1980-1984  (85)
  • 2007  (214)
  • 2005  (240)
  • 1981  (85)
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  • 2005-2009  (454)
  • 1980-1984  (85)
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  • 1
    Publication Date: 2007-04-07
    Description: Pleckstrin homology (PH) domain-mediated protein recruitment to cellular membranes is of paramount importance for signal transduction. The recruitment of many PH domains is controlled through production and turnover of their membrane ligand, phosphatidylinositol 3,4,5-trisphosphate (PIP3). We show that phosphorylation of the second messenger inositol 1,4,5-trisphosphate (IP3) into inositol 1,3,4,5-tetrakisphosphate (IP4) establishes another mode of PH domain regulation through a soluble ligand. At physiological concentrations, IP4 promoted PH domain binding to PIP3. In primary mouse CD4+CD8+ thymocytes, this was required for full activation of the protein tyrosine kinase Itk after T cell receptor engagement. Our data suggest that IP4 establishes a feedback loop of phospholipase C-gamma1 activation through Itk that is essential for T cell development.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Yina H -- Grasis, Juris A -- Miller, Andrew T -- Xu, Ruo -- Soonthornvacharin, Stephen -- Andreotti, Amy H -- Tsoukas, Constantine D -- Cooke, Michael P -- Sauer, Karsten -- AR048848/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2007 May 11;316(5826):886-9. Epub 2007 Apr 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Scripps Research Institute, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17412921" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; *Amino Acid Motifs ; Animals ; Diglycerides/metabolism ; Feedback, Physiological ; Inositol 1,4,5-Trisphosphate/metabolism ; Inositol Phosphates/*metabolism/pharmacology ; Lymphopoiesis ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Models, Biological ; Organ Culture Techniques ; Phosphatidylinositol Phosphates/metabolism ; Phospholipase C gamma/metabolism ; Phosphoproteins/metabolism ; Phosphorylation ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases/chemistry/*metabolism ; Receptors, Antigen, T-Cell/immunology ; Second Messenger Systems ; Signal Transduction ; Solubility ; T-Lymphocytes/cytology/immunology/*metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 2
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-08-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McCormick, Sheila -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):606-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Plant Gene Expression Center, USDA Agricultural Research Service-UC Berkeley, 800 Buchanan Street, Albany, CA 94710, USA. sheilamc@nature.berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17673644" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/enzymology/genetics/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; Cell Membrane/enzymology ; Crosses, Genetic ; Evolution, Molecular ; Flowers/cytology/enzymology/*physiology ; Genes, Plant ; Ligands ; Models, Biological ; Mutation ; Phosphotransferases/*genetics/*metabolism ; Pollen Tube/growth & development/*physiology ; Reproduction ; Signal Transduction ; Species Specificity
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2007-04-14
    Description: The pre-B cell receptor (pre-BCR) serves as a checkpoint in B cell development. In the 2.7 angstrom structure of a human pre-BCR Fab-like fragment, consisting of an antibody heavy chain (HC) paired with the surrogate light chain, the "unique regions" of VpreB and lambda5 replace the complementarity-determining region 3 (CDR3) loop of an antibody light chain and appear to "probe" the HC CDR3, potentially influencing the selection of the antibody repertoire. Biochemical analysis indicates that the pre-BCR is impaired in its ability to recognize antigen, which, together with electron microscopic visualization of a pre-BCR dimer, suggests ligand-independent oligomerization as the likely signaling mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bankovich, Alexander J -- Raunser, Stefan -- Juo, Z Sean -- Walz, Thomas -- Davis, Mark M -- Garcia, K Christopher -- T32 AI007290/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):291-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431183" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Complementarity Determining Regions/chemistry/physiology ; Crystallography, X-Ray ; Humans ; Immunoglobulin Heavy Chains/chemistry/physiology ; Immunoglobulin Light Chains/chemistry/physiology ; Immunoglobulin Light Chains, Surrogate ; Membrane Glycoproteins/*chemistry/physiology/ultrastructure ; Mice ; Models, Molecular ; Pre-B Cell Receptors ; Protein Conformation ; Receptors, Antigen, B-Cell/*chemistry/physiology/ultrastructure ; Recombinant Proteins ; Structure-Activity Relationship
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  • 4
    Publication Date: 2005-12-03
    Description: Macrophages and dendritic cells (DCs) are crucial for immune and inflammatory responses and belong to a network of cells that has been termed the mononuclear phagocyte system (MPS). However, the origin and lineage of these cells remain poorly understood. Here, we describe the isolation and clonal analysis of a mouse bone marrow progenitor that is specific for monocytes, several macrophage subsets, and resident spleen DCs in vivo. It was also possible to recapitulate this differentiation in vitro by using treatment with the cytokines macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Thus, macrophages and DCs appear to renew from a common progenitor, providing a cellular and molecular basis for the concept of the MPS.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fogg, Darin K -- Sibon, Claire -- Miled, Chaouki -- Jung, Steffen -- Aucouturier, Pierre -- Littman, Dan R -- Cumano, Ana -- Geissmann, Frederic -- A133856/PHS HHS/ -- G0900867/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2006 Jan 6;311(5757):83-7. Epub 2005 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM, Laboratory of Mononuclear Phagocyte Biology, Avenir Team, Necker Enfants Malades Institute, 75015 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16322423" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Lineage ; Cell Separation ; Clone Cells ; Colony-Stimulating Factors/pharmacology ; Dendritic Cells/*cytology ; Flow Cytometry ; Granulocyte Colony-Stimulating Factor/pharmacology ; Hematopoietic Stem Cell Transplantation ; Macrophage Colony-Stimulating Factor/pharmacology ; Macrophages/*cytology ; Mice ; Mice, Inbred C57BL ; Myeloid Progenitor Cells/*cytology/immunology ; Proto-Oncogene Proteins c-kit/analysis ; Receptors, Cytokine/analysis ; Receptors, HIV/analysis ; Recombinant Proteins ; Spleen/cytology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 2007-03-31
    Description: Differentiation of hepatic stellate cells (HSCs) to extracellular matrix- and growth factor-producing cells supports liver regeneration through promotion of hepatocyte proliferation. We show that the neurotrophin receptor p75NTR, a tumor necrosis factor receptor superfamily member expressed in HSCs after fibrotic and cirrhotic liver injury in humans, is a regulator of liver repair. In mice, depletion of p75NTR exacerbated liver pathology and inhibited hepatocyte proliferation in vivo. p75NTR-/- HSCs failed to differentiate to myofibroblasts and did not support hepatocyte proliferation. Moreover, inhibition of p75NTR signaling to the small guanosine triphosphatase Rho resulted in impaired HSC differentiation. Our results identify signaling from p75NTR to Rho as a mechanism for the regulation of HSC differentiation to regeneration-promoting cells that support hepatocyte proliferation in the diseased liver.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Passino, Melissa A -- Adams, Ryan A -- Sikorski, Shoana L -- Akassoglou, Katerina -- 5T32-GM07752/GM/NIGMS NIH HHS/ -- NS051470/NS/NINDS NIH HHS/ -- P30-NS047101/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 30;315(5820):1853-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of California, San Diego (UCSD), La Jolla, CA 92093-0636, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17395831" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Disease Progression ; Extracellular Matrix/metabolism ; Fibroblasts/*cytology ; Hepatocyte Growth Factor/metabolism ; Hepatocytes/*cytology ; Liver/*cytology/metabolism/pathology/physiology ; Liver Diseases/metabolism/*pathology ; *Liver Regeneration ; Mice ; Nerve Growth Factor/pharmacology ; Receptors, Nerve Growth Factor/genetics/*metabolism ; Signal Transduction ; rho GTP-Binding Proteins/metabolism
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  • 6
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-05-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Irvine, Robin -- New York, N.Y. -- Science. 2007 May 11;316(5826):845-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK. rfi20@cam.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17495162" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Inositol 1,4,5-Trisphosphate/metabolism ; Inositol Phosphates/*metabolism ; Lymphocytes/physiology ; Mice ; Phosphatidylinositol Diacylglycerol-Lyase/genetics/metabolism ; Phosphatidylinositol Phosphates/metabolism ; Phosphorylation ; Phosphotransferases (Phosphate Group Acceptor)/chemistry/genetics/metabolism ; Protein Structure, Tertiary ; Protein-Tyrosine Kinases/chemistry/*metabolism ; Receptors, Cytoplasmic and Nuclear/metabolism ; Repressor Proteins/metabolism ; Saccharomyces cerevisiae/genetics/growth & development/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Schizosaccharomyces/genetics/metabolism ; Second Messenger Systems ; *Signal Transduction ; Solubility
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 7
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-07-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Christensen, Soren Tvorup -- Ott, Carolyn Marie -- New York, N.Y. -- Science. 2007 Jul 20;317(5836):330-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Copenhagen, Copenhagen DK-2100, Denmark. stchristensen@aki.ku.dk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17641189" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Membrane/metabolism ; Cilia/*physiology ; Hedgehog Proteins/*metabolism ; Kruppel-Like Transcription Factors/metabolism ; Mice ; Receptors, Cell Surface/*metabolism ; Receptors, G-Protein-Coupled/metabolism ; *Signal Transduction ; Sterols/metabolism ; Transcription, Genetic
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 8
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chun, Jerold -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):208-10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. jchun@scripps.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431159" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Endothelium, Vascular/physiology ; Fingolimod Hydrochloride ; Humans ; Immunosuppressive Agents/pharmacology ; Lymphocytes/*physiology ; Lysophospholipids/isolation & purification/*physiology ; Mice ; Phosphotransferases (Alcohol Group Acceptor)/metabolism ; Propylene Glycols/pharmacology ; Receptors, Lysosphingolipid/metabolism ; Sphingosine/*analogs & derivatives/isolation & ; purification/pharmacology/physiology
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  • 9
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-07-07
    Description: Understanding the relationship between diversity and stability requires a knowledge of how species interact with each other and how each is affected by the environment. The relationship is also complex, because the concept of stability is multifaceted; different types of stability describing different properties of ecosystems lead to multiple diversity-stability relationships. A growing number of empirical studies demonstrate positive diversity-stability relationships. These studies, however, have emphasized only a few types of stability, and they rarely uncover the mechanisms responsible for stability. Because anthropogenic changes often affect stability and diversity simultaneously, diversity-stability relationships cannot be understood outside the context of the environmental drivers affecting both. This shifts attention away from diversity-stability relationships toward the multiple factors, including diversity, that dictate the stability of ecosystems.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ives, Anthony R -- Carpenter, Stephen R -- New York, N.Y. -- Science. 2007 Jul 6;317(5834):58-62.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Wisconsin, Madison, WI 53706, USA. arives@wisc.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17615333" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; *Ecosystem ; Environment ; Extinction, Biological ; Models, Biological ; Population Dynamics
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 10
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-03-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2007 Mar 9;315(5817):1352-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17347420" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Biomechanical Phenomena ; Extremities/innervation/physiology ; Mesencephalon/physiology ; Models, Biological ; Models, Neurological ; Muscle Contraction ; Nerve Net/*physiology ; *Robotics ; Salamandra/anatomy & histology/*physiology ; Spinal Cord/*physiology ; Swimming ; *Walking
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 11
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-02-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Firestein, Gary S -- New York, N.Y. -- Science. 2007 Feb 16;315(5814):952-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Rheumatology, Allergy and Immunology, University of California, San Diego, School of Medicine, 9500 Gilman Drive, MC 0656, La Jolla, CA 92093-0656, USA. gfirestein@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17303744" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthritis, Rheumatoid/immunology/pathology/*therapy ; Cadherins/*antagonists & inhibitors/genetics/physiology ; Disease Models, Animal ; Humans ; Mice ; Synovial Membrane/*cytology/pathology
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  • 12
    Publication Date: 2007-08-25
    Description: Most plasmalemmal proteins organize in submicrometer-sized clusters whose architecture and dynamics are still enigmatic. With syntaxin 1 as an example, we applied a combination of far-field optical nanoscopy, biochemistry, fluorescence recovery after photobleaching (FRAP) analysis, and simulations to show that clustering can be explained by self-organization based on simple physical principles. On average, the syntaxin clusters exhibit a diameter of 50 to 60 nanometers and contain 75 densely crowded syntaxins that dynamically exchange with freely diffusing molecules. Self-association depends on weak homophilic protein-protein interactions. Simulations suggest that clustering immobilizes and conformationally constrains the molecules. Moreover, a balance between self-association and crowding-induced steric repulsions is sufficient to explain both the size and dynamics of syntaxin clusters and likely of many oligomerizing membrane proteins that form supramolecular structures.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sieber, Jochen J -- Willig, Katrin I -- Kutzner, Carsten -- Gerding-Reimers, Claas -- Harke, Benjamin -- Donnert, Gerald -- Rammner, Burkhard -- Eggeling, Christian -- Hell, Stefan W -- Grubmuller, Helmut -- Lang, Thorsten -- New York, N.Y. -- Science. 2007 Aug 24;317(5841):1072-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Gottingen, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17717182" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Motifs ; Animals ; Cell Membrane/chemistry/*metabolism ; Chemistry, Physical ; Computer Simulation ; Diffusion ; Fluorescence Recovery After Photobleaching ; Green Fluorescent Proteins ; Immunoblotting ; Microscopy, Confocal ; Microscopy, Fluorescence ; Models, Biological ; Nanotechnology ; PC12 Cells ; Physicochemical Phenomena ; Protein Structure, Tertiary ; Rats ; Recombinant Fusion Proteins/chemistry/metabolism ; Syntaxin 1/*chemistry/*metabolism
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  • 13
    Publication Date: 2007-03-24
    Description: Changes in the genes encoding sensory receptor proteins are an essential step in the evolution of new sensory capacities. In primates, trichromatic color vision evolved after changes in X chromosome-linked photopigment genes. To model this process, we studied knock-in mice that expressed a human long-wavelength-sensitive (L) cone photopigment in the form of an X-linked polymorphism. Behavioral tests demonstrated that heterozygous females, whose retinas contained both native mouse pigments and human L pigment, showed enhanced long-wavelength sensitivity and acquired a new capacity for chromatic discrimination. An inherent plasticity in the mammalian visual system thus permits the emergence of a new dimension of sensory experience based solely on gene-driven changes in receptor organization.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jacobs, Gerald H -- Williams, Gary A -- Cahill, Hugh -- Nathans, Jeremy -- EY002052/EY/NEI NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 23;315(5819):1723-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Neuroscience Research Institute and Department of Psychology, University of California, Santa Barbara, CA 93106, USA. jacobs@psych.ucsb.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17379811" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Color Perception/*genetics ; Discrimination (Psychology) ; Electroretinography ; Female ; Genetic Engineering ; Heterozygote ; Humans ; Light ; Male ; Mice ; Neuronal Plasticity ; Primates/genetics/physiology ; Retinal Cone Photoreceptor Cells/*physiology ; Retinal Pigments/*genetics/*physiology ; X Chromosome/genetics ; X Chromosome Inactivation
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  • 14
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-06-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fitzgerald, Katherine A -- Golenbock, Douglas T -- New York, N.Y. -- Science. 2007 Jun 15;316(5831):1574-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA. kate.fitzgerald@umassmed.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17569850" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/metabolism ; Adaptor Proteins, Vesicular Transport/metabolism ; *Adjuvants, Immunologic ; Animals ; Crystallography, X-Ray ; Glycolipids/chemistry/metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Lipid A/*analogs & derivatives/chemistry/immunology/metabolism ; Lymphocyte Activation ; Lymphocyte Antigen 96/*chemistry/metabolism ; Mice ; Phosphates/metabolism ; Protein Conformation ; Receptors, Interleukin/metabolism ; Signal Transduction ; T-Lymphocytes/immunology ; Toll-Like Receptor 4/chemistry/*immunology/metabolism
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  • 15
    Publication Date: 2007-03-31
    Description: Plastid-to-nucleus retrograde signaling coordinates nuclear gene expression with chloroplast function and is essential for the photoautotrophic life-style of plants. Three retrograde signals have been described, but little is known of their signaling pathways. We show here that GUN1, a chloroplast-localized pentatricopeptide-repeat protein, and ABI4, an Apetala 2 (AP2)-type transcription factor, are common to all three pathways. ABI4 binds the promoter of a retrograde-regulated gene through a conserved motif found in close proximity to a light-regulatory element. We propose a model in which multiple indicators of aberrant plastid function in Arabidopsis are integrated upstream of GUN1 within plastids, which leads to ABI4-mediated repression of nuclear-encoded genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Koussevitzky, Shai -- Nott, Ajit -- Mockler, Todd C -- Hong, Fangxin -- Sachetto-Martins, Gilberto -- Surpin, Marci -- Lim, Jason -- Mittler, Ron -- Chory, Joanne -- DRG-1865-05/PHS HHS/ -- F32 GM 18172/GM/NIGMS NIH HHS/ -- F32 GM 69090/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 May 4;316(5825):715-9. Epub 2007 Mar 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17395793" target="_blank"〉PubMed〈/a〉
    Keywords: Abscisic Acid ; Amino Acid Motifs ; Amino Acid Sequence ; Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Cell Nucleus/*metabolism/*microbiology ; Chloroplasts/*metabolism ; DNA, Plant/metabolism ; DNA-Binding Proteins/chemistry/genetics/*metabolism ; Electron Transport ; *Gene Expression Regulation, Plant ; Light-Harvesting Protein Complexes/genetics ; Lincomycin/pharmacology ; Models, Biological ; Molecular Sequence Data ; Oligonucleotide Array Sequence Analysis ; Plants, Genetically Modified ; Promoter Regions, Genetic ; Protoporphyrins/metabolism ; Pyridazines/pharmacology ; Signal Transduction ; Transcription Factors/*metabolism
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  • 16
    Publication Date: 2007-07-07
    Description: The in vivo potential of neural stem cells in the postnatal mouse brain is not known, but because they produce many different types of neurons, they must be either very versatile or very diverse. By specifically targeting stem cells and following their progeny in vivo, we showed that postnatal stem cells in different regions produce different types of neurons, even when heterotopically grafted or grown in culture. This suggests that rather than being plastic and homogeneous, neural stem cells are a restricted and diverse population of progenitors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Merkle, Florian T -- Mirzadeh, Zaman -- Alvarez-Buylla, Arturo -- New York, N.Y. -- Science. 2007 Jul 20;317(5836):381-4. Epub 2007 Jul 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neurosurgery and Developmental and Stem Cell Biology Program, University of California, San Francisco, San Francisco, CA 94143-0525, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17615304" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology ; Animals ; Animals, Newborn ; Astrocytes/cytology ; Brain/*cytology ; Cell Differentiation ; Cells, Cultured ; Interneurons/cytology ; Lateral Ventricles/cytology ; Mice ; Neuroglia/cytology ; Neurons/*cytology ; Olfactory Bulb/cytology ; Stem Cell Transplantation ; Transplantation, Heterotopic
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  • 17
    Publication Date: 2007-08-19
    Description: In Gram-negative bacteria and eukaryotic organelles, beta-barrel proteins of the outer membrane protein 85-two-partner secretion B (Omp85-TpsB) superfamily are essential components of protein transport machineries. The TpsB transporter FhaC mediates the secretion of Bordetella pertussis filamentous hemagglutinin (FHA). We report the 3.15 A crystal structure of FhaC. The transporter comprises a 16-stranded beta barrel that is occluded by an N-terminal alpha helix and an extracellular loop and a periplasmic module composed of two aligned polypeptide-transport-associated (POTRA) domains. Functional data reveal that FHA binds to the POTRA 1 domain via its N-terminal domain and likely translocates the adhesin-repeated motifs in an extended hairpin conformation, with folding occurring at the cell surface. General features of the mechanism obtained here are likely to apply throughout the superfamily.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Clantin, Bernard -- Delattre, Anne-Sophie -- Rucktooa, Prakash -- Saint, Nathalie -- Meli, Albano C -- Locht, Camille -- Jacob-Dubuisson, Francoise -- Villeret, Vincent -- New York, N.Y. -- Science. 2007 Aug 17;317(5840):957-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉UMR8161 CNRS, Institut de Biologie de Lille, Universite de Lille 1, Universite de Lille 2, 1 rue du Prof. Calmette, F-59021 Lille cedex, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17702945" target="_blank"〉PubMed〈/a〉
    Keywords: Adhesins, Bacterial/chemistry/*metabolism ; Amino Acid Motifs ; Amino Acid Sequence ; Bacterial Outer Membrane Proteins/*chemistry/genetics/*metabolism ; Bordetella pertussis/*chemistry/metabolism ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Hydrophobic and Hydrophilic Interactions ; Lipid Bilayers/chemistry/metabolism ; Membrane Transport Proteins/chemistry/metabolism ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Transport ; Virulence Factors, Bordetella/chemistry/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 18
    Publication Date: 2007-03-31
    Description: A marine ecosystem model seeded with many phytoplankton types, whose physiological traits were randomly assigned from ranges defined by field and laboratory data, generated an emergent community structure and biogeography consistent with observed global phytoplankton distributions. The modeled organisms included types analogous to the marine cyanobacterium Prochlorococcus. Their emergent global distributions and physiological properties simultaneously correspond to observations. This flexible representation of community structure can be used to explore relations between ecosystems, biogeochemical cycles, and climate change.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Follows, Michael J -- Dutkiewicz, Stephanie -- Grant, Scott -- Chisholm, Sallie W -- New York, N.Y. -- Science. 2007 Mar 30;315(5820):1843-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth, Atmospheric and Planetary Sciences, Massachusetts Institute of Technology, 54-1514 MIT, Cambridge, MA 02139, USA. mick@mit.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17395828" target="_blank"〉PubMed〈/a〉
    Keywords: Biomass ; Computer Simulation ; *Ecosystem ; Geography ; Light ; Mathematics ; Models, Biological ; Oceans and Seas ; Phytoplankton/growth & development/*physiology ; Prochlorococcus/growth & development/*physiology ; Seawater/*microbiology ; Temperature
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  • 19
    Publication Date: 2007-11-03
    Description: The limb blastemal cells of an adult salamander regenerate the structures distal to the level of amputation, and the surface protein Prod 1 is a critical determinant of their proximodistal identity. The anterior gradient protein family member nAG is a secreted ligand for Prod 1 and a growth factor for cultured newt blastemal cells. nAG is sequentially expressed after amputation in the regenerating nerve and the wound epidermis-the key tissues of the stem cell niche-and its expression in both locations is abrogated by denervation. The local expression of nAG after electroporation is sufficient to rescue a denervated blastema and regenerate the distal structures. Our analysis brings together the positional identity of the blastema and the classical nerve dependence of limb regeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696928/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696928/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kumar, Anoop -- Godwin, James W -- Gates, Phillip B -- Garza-Garcia, A Acely -- Brockes, Jeremy P -- G0600229/Medical Research Council/United Kingdom -- G0600229(77696)/Medical Research Council/United Kingdom -- G9537983/Medical Research Council/United Kingdom -- G9537983(56733)/Medical Research Council/United Kingdom -- MC_U117574559/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):772-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17975060" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD59/*physiology ; COS Cells ; Cells, Cultured ; Cercopithecus aethiops ; Denervation ; Extremities/innervation ; Glycosylphosphatidylinositols/physiology ; Growth Substances ; Intercellular Signaling Peptides and Proteins/isolation & ; purification/*physiology/secretion ; Ligands ; Mice ; Notophthalmus viridescens ; Peripheral Nerves/*physiology ; Regeneration/*physiology ; Stem Cells/*cytology ; Two-Hybrid System Techniques
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  • 20
    Publication Date: 2007-02-03
    Description: The 66-kilodalton isoform of the growth factor adapter Shc (p66Shc) translates oxidative damage into cell death by acting as reactive oxygen species (ROS) producer within mitochondria. However, the signaling link between cellular stress and mitochondrial proapoptotic activity of p66Shc was not known. We demonstrate that protein kinase C beta, activated by oxidative conditions in the cell, induces phosphorylation of p66Shc and triggers mitochondrial accumulation of the protein after it is recognized by the prolyl isomerase Pin1. Once imported, p66Shc causes alterations of mitochondrial Ca2+ responses and three-dimensional structure, thus inducing apoptosis. These data identify a signaling route that activates an apoptotic inducer shortening the life span and could be a potential target of pharmacological approaches to inhibit aging.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pinton, Paolo -- Rimessi, Alessandro -- Marchi, Saverio -- Orsini, Francesca -- Migliaccio, Enrica -- Giorgio, Marco -- Contursi, Cristina -- Minucci, Saverio -- Mantovani, Fiamma -- Wieckowski, Mariusz R -- Del Sal, Giannino -- Pelicci, Pier Giuseppe -- Rizzuto, Rosario -- GGP05284/Telethon/Italy -- New York, N.Y. -- Science. 2007 Feb 2;315(5812):659-63.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Experimental and Diagnostic Medicine, Section of General Pathology and Interdisciplinary Center for the Study of Inflammation (ICSI), University of Ferrara, Ferrera, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272725" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Adenosine Triphosphate/metabolism/pharmacology ; Animals ; *Apoptosis ; Calcium/metabolism ; Calcium Signaling ; *Cell Aging ; Cell Survival ; Cells, Cultured ; Cyclosporine/pharmacology ; Hydrogen Peroxide/metabolism/pharmacology ; Mice ; Mitochondria/*metabolism/ultrastructure ; Mutation ; Oxidative Stress ; Peptidylprolyl Isomerase/*metabolism ; Permeability ; Phosphorylation ; Protein Kinase C/antagonists & inhibitors/genetics/*metabolism ; Protein Kinase C beta ; Reactive Oxygen Species/metabolism ; Recombinant Fusion Proteins/metabolism ; Shc Signaling Adaptor Proteins ; *Signal Transduction
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  • 21
    Publication Date: 2007-05-26
    Description: Telford et al. (Brevia, 19 May 2006, p. 1015) reported that freshwater diatoms exhibit regional-scale richness-pH relationships that depend substantially on regional habitat availability. On this basis, the authors argued that, despite their microscopic size, diatoms are not ubiquitously dispersed. Here, I describe my demonstration that their primary evidence against the ubiquitous dispersal hypothesis is spurious.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pither, Jason -- New York, N.Y. -- Science. 2007 May 25;316(5828):1124; author reply 1124.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of Arizona, BSW 310, 1041 East Lowell Street, Tucson, AZ 85721, USA. pitherj@email.arizona.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17525319" target="_blank"〉PubMed〈/a〉
    Keywords: Biodiversity ; Diatoms/*physiology ; *Ecosystem ; *Environmental Microbiology ; Europe ; Fresh Water ; Hydrogen-Ion Concentration ; Models, Biological ; North America ; Water Microbiology
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  • 22
    Publication Date: 2007-02-10
    Description: A central issue in the regulation of apoptosis by the Bcl-2 family is whether its BH3-only members initiate apoptosis by directly binding to the essential cell-death mediators Bax and Bak, or whether they can act indirectly, by engaging their pro-survival Bcl-2-like relatives. Contrary to the direct-activation model, we show that Bax and Bak can mediate apoptosis without discernable association with the putative BH3-only activators (Bim, Bid, and Puma), even in cells with no Bim or Bid and reduced Puma. Our results indicate that BH3-only proteins induce apoptosis at least primarily by engaging the multiple pro-survival relatives guarding Bax and Bak.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Willis, Simon N -- Fletcher, Jamie I -- Kaufmann, Thomas -- van Delft, Mark F -- Chen, Lin -- Czabotar, Peter E -- Ierino, Helen -- Lee, Erinna F -- Fairlie, W Douglas -- Bouillet, Philippe -- Strasser, Andreas -- Kluck, Ruth M -- Adams, Jerry M -- Huang, David C S -- CA43540/CA/NCI NIH HHS/ -- CA80188/CA/NCI NIH HHS/ -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2007 Feb 9;315(5813):856-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17289999" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Apoptosis ; Apoptosis Regulatory Proteins/chemistry/genetics/*metabolism ; BH3 Interacting Domain Death Agonist Protein/chemistry/genetics/*metabolism ; Cell Line ; Cells, Cultured ; Humans ; Ligands ; Membrane Proteins/chemistry/genetics/*metabolism ; Mice ; Mice, Knockout ; Models, Biological ; Mutation ; Myeloid Cell Leukemia Sequence 1 Protein ; Neoplasm Proteins/metabolism ; Protein Structure, Tertiary ; Proteins/metabolism ; Proto-Oncogene Proteins/chemistry/genetics/*metabolism ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; Tumor Suppressor Proteins/genetics/metabolism ; bcl-2 Homologous Antagonist-Killer Protein/metabolism ; bcl-2-Associated X Protein/chemistry/*metabolism ; bcl-Associated Death Protein/metabolism ; bcl-X Protein/metabolism
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  • 23
    Publication Date: 2007-05-26
    Description: The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB(1) cannabinoid receptors (CB(1)Rs) are enriched in the axonal growth cones of gamma-aminobutyric acid-containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB(1)R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB(1)Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Berghuis, Paul -- Rajnicek, Ann M -- Morozov, Yury M -- Ross, Ruth A -- Mulder, Jan -- Urban, Gabriella M -- Monory, Krisztina -- Marsicano, Giovanni -- Matteoli, Michela -- Canty, Alison -- Irving, Andrew J -- Katona, Istvan -- Yanagawa, Yuchio -- Rakic, Pasko -- Lutz, Beat -- Mackie, Ken -- Harkany, Tibor -- DA00286/DA/NIDA NIH HHS/ -- DA015916/DA/NIDA NIH HHS/ -- DA11322/DA/NIDA NIH HHS/ -- New York, N.Y. -- Science. 2007 May 25;316(5828):1212-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-17177 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17525344" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/physiology ; Cannabinoid Receptor Modulators/metabolism/*physiology ; Cell Movement ; Cells, Cultured ; Cerebral Cortex/cytology/embryology/ultrastructure ; *Endocannabinoids ; Growth Cones/physiology/ultrasonography ; In Situ Hybridization ; Interneurons/metabolism/*physiology/ultrasonography ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1/agonists/*physiology ; Signal Transduction ; Stem Cells/metabolism ; Synapses/physiology/ultrasonography ; Xenopus Proteins/physiology ; Xenopus laevis ; gamma-Aminobutyric Acid/metabolism
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  • 24
    Publication Date: 2007-04-21
    Description: The mechanisms controlling the establishment of the embryonic-abembryonic (E-Ab) axis of the mammalian blastocyst are controversial. We used in vitro time-lapse imaging and in vivo lineage labeling to provide evidence that the E-Ab axis of the mouse blastocyst is generated independently of early cell lineage. Rather, both the boundary between two-cell blastomeres and the E-Ab axis of the blastocyst align relative to the ellipsoidal shape of the zona pellucida (ZP), an extraembryonic structure. Lack of correlation between cell lineage and the E-Ab axis can be explained by the rotation of the embryo within the ZP.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kurotaki, Yoko -- Hatta, Kohei -- Nakao, Kazuki -- Nabeshima, Yo-Ichi -- Fujimori, Toshihiko -- New York, N.Y. -- Science. 2007 May 4;316(5825):719-23. Epub 2007 Apr 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17446354" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blastocyst/*cytology/physiology ; Blastocyst Inner Cell Mass ; Blastomeres/*physiology ; Body Patterning ; Cell Lineage ; Cell Movement ; Cell Nucleus/physiology ; *Embryonic Development ; Green Fluorescent Proteins ; Image Processing, Computer-Assisted ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microscopy, Fluorescence ; Motion Pictures as Topic ; Rotation ; Zona Pellucida/physiology/*ultrastructure
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  • 25
    Publication Date: 2007-01-20
    Description: The Staphylococcus aureus Panton-Valentine leukocidin (PVL) is a pore-forming toxin secreted by strains epidemiologically associated with the current outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) and with the often-lethal necrotizing pneumonia. To investigate the role of PVL in pulmonary disease, we tested the pathogenicity of clinical isolates, isogenic PVL-negative and PVL-positive S. aureus strains, as well as purified PVL, in a mouse acute pneumonia model. Here we show that PVL is sufficient to cause pneumonia and that the expression of this leukotoxin induces global changes in transcriptional levels of genes encoding secreted and cell wall-anchored staphylococcal proteins, including the lung inflammatory factor staphylococcal protein A (Spa).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Labandeira-Rey, Maria -- Couzon, Florence -- Boisset, Sandrine -- Brown, Eric L -- Bes, Michele -- Benito, Yvonne -- Barbu, Elena M -- Vazquez, Vanessa -- Hook, Magnus -- Etienne, Jerome -- Vandenesch, Francois -- Bowden, M Gabriela -- AI020624/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Feb 23;315(5815):1130-3. Epub 2007 Jan 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Extracellular Matrix Biology, Institute of Biosciences and Technology, Texas A&M University System Health Science Center, Houston, TX 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17234914" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins/genetics/metabolism ; Bacterial Toxins/genetics ; Calcium-Binding Proteins/genetics/metabolism ; Disease Models, Animal ; Exotoxins/genetics/*physiology ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Hemorrhage ; Leukocidins/genetics/*physiology ; Lung/microbiology/*pathology ; Methicillin Resistance ; Mice ; Mice, Inbred BALB C ; Necrosis ; Oligonucleotide Array Sequence Analysis ; Pneumonia, Staphylococcal/*microbiology/*pathology ; Staphylococcal Protein A/genetics/*metabolism ; Staphylococcus aureus/genetics/growth & development/metabolism/*pathogenicity ; Transcription, Genetic ; Virulence ; Virulence Factors/genetics/*physiology
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  • 26
    Publication Date: 2007-05-26
    Description: Mutations affecting the BRCT domains of the breast cancer-associated tumor suppressor BRCA1 disrupt the recruitment of this protein to DNA double-strand breaks (DSBs). The molecular structures at DSBs recognized by BRCA1 are presently unknown. We report the interaction of the BRCA1 BRCT domain with RAP80, a ubiquitin-binding protein. RAP80 targets a complex containing the BRCA1-BARD1 (BRCA1-associated ring domain protein 1) E3 ligase and the deubiquitinating enzyme (DUB) BRCC36 to MDC1-gammaH2AX-dependent lysine(6)- and lysine(63)-linked ubiquitin polymers at DSBs. These events are required for cell cycle checkpoint and repair responses to ionizing radiation, implicating ubiquitin chain recognition and turnover in the BRCA1-mediated repair of DSBs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706583/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2706583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sobhian, Bijan -- Shao, Genze -- Lilli, Dana R -- Culhane, Aedin C -- Moreau, Lisa A -- Xia, Bing -- Livingston, David M -- Greenberg, Roger A -- K08 CA106597/CA/NCI NIH HHS/ -- K08 CA106597-01A2/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 May 25;316(5828):1198-202.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Dana-Farber Cancer Institute and Department of Genetics and Department of Medicine, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17525341" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; BRCA1 Protein/*metabolism ; Binding Sites ; Carrier Proteins/*metabolism ; Cell Line ; DNA/*metabolism ; *DNA Breaks, Double-Stranded ; DNA Repair/physiology ; HeLa Cells ; Humans ; Mice ; Molecular Sequence Data ; Nuclear Proteins/*metabolism ; Nucleic Acid Conformation ; Protein Structure, Tertiary ; Tumor Suppressor Proteins/metabolism ; Ubiquitin/*metabolism ; Ubiquitin-Protein Ligases/metabolism
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  • 27
    Publication Date: 2007-10-13
    Description: Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wood, Laura D -- Parsons, D Williams -- Jones, Sian -- Lin, Jimmy -- Sjoblom, Tobias -- Leary, Rebecca J -- Shen, Dong -- Boca, Simina M -- Barber, Thomas -- Ptak, Janine -- Silliman, Natalie -- Szabo, Steve -- Dezso, Zoltan -- Ustyanksky, Vadim -- Nikolskaya, Tatiana -- Nikolsky, Yuri -- Karchin, Rachel -- Wilson, Paul A -- Kaminker, Joshua S -- Zhang, Zemin -- Croshaw, Randal -- Willis, Joseph -- Dawson, Dawn -- Shipitsin, Michail -- Willson, James K V -- Sukumar, Saraswati -- Polyak, Kornelia -- Park, Ben Ho -- Pethiyagoda, Charit L -- Pant, P V Krishna -- Ballinger, Dennis G -- Sparks, Andrew B -- Hartigan, James -- Smith, Douglas R -- Suh, Erick -- Papadopoulos, Nickolas -- Buckhaults, Phillip -- Markowitz, Sanford D -- Parmigiani, Giovanni -- Kinzler, Kenneth W -- Velculescu, Victor E -- Vogelstein, Bert -- CA 43460/CA/NCI NIH HHS/ -- CA 57345/CA/NCI NIH HHS/ -- CA109274/CA/NCI NIH HHS/ -- CA112828/CA/NCI NIH HHS/ -- CA121113/CA/NCI NIH HHS/ -- CA62924/CA/NCI NIH HHS/ -- GM070219/GM/NIGMS NIH HHS/ -- GM07309/GM/NIGMS NIH HHS/ -- P30-CA43703/CA/NCI NIH HHS/ -- RR017698/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 16;318(5853):1108-13. Epub 2007 Oct 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ludwig Center for Cancer Genetics and Therapeutics and Howard Hughes Medical Institute at Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17932254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breast Neoplasms/*genetics/metabolism ; Cell Line ; Chromosome Mapping ; Colorectal Neoplasms/*genetics/metabolism ; Computational Biology ; DNA, Neoplasm ; Databases, Genetic ; Genes, Neoplasm ; Genome, Human ; Humans ; Metabolic Networks and Pathways/genetics ; Mice ; Mutation ; Neoplasm Proteins/genetics/metabolism ; Sequence Analysis, DNA
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  • 28
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-09-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2007 Sep 7;317(5843):1305.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17823319" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/*therapeutic use ; Clinical Trials as Topic ; HIV Protease Inhibitors/*therapeutic use ; Humans ; Mice ; Nelfinavir/therapeutic use
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  • 29
    Publication Date: 2007-02-17
    Description: Migrating cells extend protrusions, probing the surrounding matrix in search of permissive sites to form adhesions. We found that actin fibers polymerizing along the leading edge directed local protrusions and drove synchronous sideways movement of beta1 integrin adhesion receptors. These movements lead to the clustering and positioning of conformationally activated, but unligated, beta1 integrins along the leading edge of fibroblast lamellae and growth cone filopodia. Thus, rapid actin-based movement of primed integrins along the leading edge suggests a "sticky fingers" mechanism to probe for new adhesion sites and to direct migration.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Galbraith, Catherine G -- Yamada, Kenneth M -- Galbraith, James A -- New York, N.Y. -- Science. 2007 Feb 16;315(5814):992-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17303755" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*physiology ; Animals ; Antigens, CD29/*physiology ; Cell Adhesion/*physiology ; Cell Adhesion Molecules/metabolism ; Cell Line ; Cell Movement/*physiology ; Extracellular Matrix/metabolism ; Fibroblasts/physiology ; Fibronectins/metabolism ; Green Fluorescent Proteins/metabolism ; Mice ; Microfilament Proteins/metabolism ; NIH 3T3 Cells ; Phosphoproteins/metabolism ; Protein Binding ; Pseudopodia/metabolism
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  • 30
    Publication Date: 2007-09-22
    Description: Platelets are generated from megakaryocytes (MKs) in mammalian bone marrow (BM) by mechanisms that remain poorly understood. Here we describe the use of multiphoton intravital microscopy in intact BM to visualize platelet generation in mice. MKs were observed as sessile cells that extended dynamic proplatelet-like protrusions into microvessels. These intravascular extensions appeared to be sheared from their transendothelial stems by flowing blood, resulting in the appearance of proplatelets in peripheral blood. In vitro, proplatelet production from differentiating MKs was enhanced by fluid shear. These results confirm the concept of proplatelet formation in vivo and are consistent with the possibility that blood flow-induced hydrodynamic shear stress is a biophysical determinant of thrombopoiesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Junt, Tobias -- Schulze, Harald -- Chen, Zhao -- Massberg, Steffen -- Goerge, Tobias -- Krueger, Andreas -- Wagner, Denisa D -- Graf, Thomas -- Italiano, Joseph E Jr -- Shivdasani, Ramesh A -- von Andrian, Ulrich H -- HL068130/HL/NHLBI NIH HHS/ -- HL56949/HL/NHLBI NIH HHS/ -- HL63143/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2007 Sep 21;317(5845):1767-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immune Disease Institute and Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17885137" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Proteins ; Blood Platelets/*cytology ; Bone Marrow/*physiology ; Cells, Cultured ; Luminescent Proteins ; Megakaryocytes/*cytology ; Mice ; Microscopy, Fluorescence, Multiphoton ; Platelet Membrane Glycoprotein IIb ; Shear Strength ; Thrombopoiesis/*physiology
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  • 31
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-05-26
    Description: Single-molecule force experiments in vitro enable the characterization of the mechanical response of biological matter at the nanometer scale. However, they do not reveal the molecular mechanisms underlying mechanical function. These can only be readily studied through molecular dynamics simulations of atomic structural models: "in silico" (by computer analysis) single-molecule experiments. Steered molecular dynamics simulations, in which external forces are used to explore the response and function of macromolecules, have become a powerful tool complementing and guiding in vitro single-molecule experiments. The insights provided by in silico experiments are illustrated here through a review of recent research in three areas of protein mechanics: elasticity of the muscle protein titin and the extracellular matrix protein fibronectin; linker-mediated elasticity of the cytoskeleton protein spectrin; and elasticity of ankyrin repeats, a protein module found ubiquitously in cells but with an as-yet unclear function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sotomayor, Marcos -- Schulten, Klaus -- 1 R01 GM073655/GM/NIGMS NIH HHS/ -- P41 RR05969/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2007 May 25;316(5828):1144-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physics, University of Illinois at Urbana-Champaign, and Beckman Institute for Advanced Science and Technology, 405 North Mathews Avenue, Urbana, IL 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17525328" target="_blank"〉PubMed〈/a〉
    Keywords: Ankyrin Repeat/*physiology ; Computer Simulation ; Connectin ; Elasticity ; Fibronectins/*physiology ; Humans ; Models, Biological ; Muscle Proteins/*physiology ; Protein Kinases/*physiology ; Spectrin/*physiology ; Spectrum Analysis/*methods
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-08-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):612-4.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17673648" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD34/analysis ; CD4-Positive T-Lymphocytes/immunology/virology ; Clinical Trials as Topic ; *Genetic Therapy ; Genetic Vectors ; HIV/genetics/immunology ; HIV Antibodies/genetics/immunology ; HIV Infections/*immunology/*therapy ; Hematopoietic Stem Cells/immunology ; Humans ; *Immunotherapy ; Mice ; Transduction, Genetic
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-02-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kahl, Barbara C -- Peters, Georg -- New York, N.Y. -- Science. 2007 Feb 23;315(5815):1082-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Medical Microbiology, University of Munster, Domagkstrasse 10, D-49149 Munster, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17322047" target="_blank"〉PubMed〈/a〉
    Keywords: Adhesins, Bacterial/genetics/metabolism ; Animals ; Bacterial Toxins/analysis ; Exotoxins/analysis/*physiology ; Gene Expression Regulation, Bacterial ; Hemorrhage ; Leukocidins/analysis/*physiology ; Lung/chemistry/microbiology/*pathology ; Methicillin Resistance ; Mice ; Models, Biological ; Necrosis ; Phagocytosis ; Pneumonia, Staphylococcal/*microbiology/*pathology ; Respiratory Mucosa/microbiology ; Staphylococcal Protein A/genetics/*metabolism ; Staphylococcus aureus/genetics/growth & development/metabolism/*pathogenicity ; Virulence Factors/analysis/*physiology
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  • 34
    Publication Date: 2007-10-13
    Description: The catalytic (C) subunit of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is inhibited by two classes of regulatory subunits, RI and RII. The RII subunits are substrates as well as inhibitors and do not require adenosine triphosphate (ATP) to form holoenzyme, which distinguishes them from RI subunits. To understand the molecular basis for isoform diversity, we solved the crystal structure of an RIIalpha holoenzyme and compared it to the RIalpha holoenzyme. Unphosphorylated RIIalpha(90-400), a deletion mutant, undergoes major conformational changes as both of the cAMP-binding domains wrap around the C subunit's large lobe. The hallmark of this conformational reorganization is the helix switch in domain A. The C subunit is in an open conformation, and its carboxyl-terminal tail is disordered. This structure demonstrates the conserved and isoform-specific features of RI and RII and the importance of ATP, and also provides a new paradigm for designing isoform-specific activators or antagonists for PKA.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036697/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4036697/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Jian -- Brown, Simon H J -- von Daake, Sventja -- Taylor, Susan S -- GM34921/GM/NIGMS NIH HHS/ -- R01 GM034921/GM/NIGMS NIH HHS/ -- R01 GM034921-23/GM/NIGMS NIH HHS/ -- T32-CA009524/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 Oct 12;318(5848):274-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17932298" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Amino Acid Motifs ; Animals ; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinase RIIalpha Subunit ; Cyclic AMP-Dependent Protein Kinase RIalpha Subunit ; Cyclic AMP-Dependent Protein Kinases/*chemistry/genetics/metabolism ; Holoenzymes/chemistry ; Hydrophobic and Hydrophilic Interactions ; Isoenzymes/chemistry ; Mice ; Models, Molecular ; Protein Conformation ; Protein Structure, Secondary ; Protein Structure, Tertiary
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  • 35
    Publication Date: 2007-06-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wu, Jiang I -- Crabtree, Gerald R -- New York, N.Y. -- Science. 2007 Jun 22;316(5832):1710-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howared Hughes Medical Institute and Stanford University School of Medicine, Stanford, CA 94305-5323, USA. crabtree@cmgm.stanford.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17588921" target="_blank"〉PubMed〈/a〉
    Keywords: Actins/*physiology ; Animals ; Cell Nucleus/*physiology ; Cell Shape/physiology ; Gene Expression Regulation ; Mice ; Protein Transport ; Serum Response Factor/physiology ; Signal Transduction/*physiology ; Trans-Activators/*physiology ; Transcription, Genetic/physiology
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  • 36
    Publication Date: 2007-01-27
    Description: Primary pneumonic plague is transmitted easily, progresses rapidly, and causes high mortality, but the mechanisms by which Yersinia pestis overwhelms the lungs are largely unknown. We show that the plasminogen activator Pla is essential for Y. pestis to cause primary pneumonic plague but is less important for dissemination during pneumonic plague than during bubonic plague. Experiments manipulating its temporal expression showed that Pla allows Y. pestis to replicate rapidly in the airways, causing a lethal fulminant pneumonia; if unexpressed, inflammation is aborted, and lung repair is activated. Inhibition of Pla expression prolonged the survival of animals with the disease, offering a therapeutic option to extend the period during which antibiotics are effective.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lathem, Wyndham W -- Price, Paul A -- Miller, Virginia L -- Goldman, William E -- AI53298/AI/NIAID NIH HHS/ -- DK52574/DK/NIDDK NIH HHS/ -- F32 AI069688-01/AI/NIAID NIH HHS/ -- NRSA T32 GM07067/GM/NIGMS NIH HHS/ -- U54 AI057160/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Jan 26;315(5811):509-13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17255510" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Proliferation ; Colony Count, Microbial ; Cytokines/genetics/metabolism ; Female ; Fibrinogen/metabolism ; Gene Expression Regulation ; Gene Expression Regulation, Bacterial ; Lung/immunology/*microbiology/pathology ; Mice ; Mice, Inbred C57BL ; Mutation ; Plague/immunology/*microbiology/pathology ; Plasminogen/metabolism ; Plasminogen Activators/genetics/*metabolism ; Pneumonia, Bacterial/immunology/*microbiology/pathology ; Spleen/microbiology ; Tetracyclines/pharmacology ; Virulence Factors/genetics/metabolism ; Yersinia pestis/enzymology/genetics/growth & development/*pathogenicity
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  • 37
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-05-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gatfield, David -- Schibler, Ueli -- New York, N.Y. -- Science. 2007 May 25;316(5828):1135-6. Epub 2007 May 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology and NCCR Frontiers in Genetics, Sciences III, University of Geneva, CH-1211 Geneva-4, Switzerland. david.gatfield@molbio.unige.ch〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17495136" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Cycle Proteins/physiology ; Circadian Rhythm/genetics/*physiology ; Cryptochromes ; F-Box Proteins/physiology ; Flavoproteins/physiology ; Mice ; Nuclear Proteins/physiology ; Period Circadian Proteins ; Phenotype ; Proteasome Endopeptidase Complex/*physiology ; Transcription Factors/physiology
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  • 38
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Proud, Christopher G -- New York, N.Y. -- Science. 2007 Nov 9;318(5852):926-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17991850" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/metabolism ; Cells, Cultured ; Guanosine Triphosphate/metabolism ; Humans ; Insulin/metabolism ; Models, Biological ; Monomeric GTP-Binding Proteins/*metabolism ; Multiprotein Complexes ; Neuropeptides/*metabolism ; Protein Binding ; Protein Kinases/*metabolism ; Proteins ; *Signal Transduction ; Sirolimus/metabolism/pharmacology ; TOR Serine-Threonine Kinases ; Tacrolimus Binding Protein 1A/metabolism ; Tacrolimus Binding Proteins/antagonists & inhibitors/*metabolism ; Transcription Factors/*metabolism
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-09-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geddis, Amy E -- Kaushansky, Kenneth -- New York, N.Y. -- Science. 2007 Sep 21;317(5845):1689-91.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Pediatrics and Medicine, University of California, San Diego, CA 92103-8811, USA. kkaushansky@ucsd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17885117" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Animals ; Blood Platelets/*cytology ; Humans ; Megakaryocytes/*cytology ; Mice ; Thrombopoiesis/*physiology
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  • 40
    Publication Date: 2007-02-10
    Description: The bacterium Myxococcus xanthus has two motility systems: S motility, which is powered by type IV pilus retraction, and A motility, which is powered by unknown mechanism(s). We found that A motility involved transient adhesion complexes that remained at fixed positions relative to the substratum as cells moved forward. Complexes assembled at leading cell poles and dispersed at the rear of the cells. When cells reversed direction, the A-motility clusters relocalized to the new leading poles together with S-motility proteins. The Frz chemosensory system coordinated the two motility systems. The dynamics of protein cluster localization suggest that intracellular motors and force transmission by dynamic focal adhesions can power bacterial motility.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095873/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095873/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mignot, Tam -- Shaevitz, Joshua W -- Hartzell, Patricia L -- Zusman, David R -- GM20509/GM/NIGMS NIH HHS/ -- R01 GM020509/GM/NIGMS NIH HHS/ -- R01 GM075242-03/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Feb 9;315(5813):853-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. tmignot@berkeley.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17289998" target="_blank"〉PubMed〈/a〉
    Keywords: Anti-Bacterial Agents/pharmacology ; *Bacterial Adhesion ; Bacterial Proteins/analysis/genetics/metabolism/*physiology ; Cephalexin/pharmacology ; Fimbriae, Bacterial/physiology ; Focal Adhesions/*physiology ; Luminescent Proteins ; Models, Biological ; Molecular Motor Proteins/analysis/genetics/*physiology ; Movement ; Myxococcus xanthus/cytology/genetics/*physiology ; Recombinant Fusion Proteins/analysis
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  • 41
    Publication Date: 2007-08-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2007 Aug 17;317(5840):884-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17702917" target="_blank"〉PubMed〈/a〉
    Keywords: *Advisory Committees ; Animals ; Benzhydryl Compounds ; Child ; Endocrine Disruptors/administration & dosage/*toxicity ; Female ; Humans ; Male ; Mice ; Phenols/administration & dosage/*toxicity ; Pregnancy ; United States
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  • 42
    Publication Date: 2007-11-03
    Description: During pregnancy, maternal pancreatic islets grow to match dynamic physiological demands, but the mechanisms regulating adaptive islet growth in this setting are poorly understood. Here we show that menin, a protein previously characterized as an endocrine tumor suppressor and transcriptional regulator, controls islet growth in pregnant mice. Pregnancy stimulated proliferation of maternal pancreatic islet beta-cells that was accompanied by reduced islet levels of menin and its targets. Transgenic expression of menin in maternal beta-cells prevented islet expansion and led to hyperglycemia and impaired glucose tolerance, hallmark features of gestational diabetes. Prolactin, a hormonal regulator of pregnancy, repressed islet menin levels and stimulated beta-cell proliferation. These results expand our understanding of mechanisms underlying diabetes pathogenesis and reveal potential targets for therapy in diabetes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Karnik, Satyajit K -- Chen, Hainan -- McLean, Graeme W -- Heit, Jeremy J -- Gu, Xueying -- Zhang, Andrew Y -- Fontaine, Magali -- Yen, Michael H -- Kim, Seung K -- T32DK007217-32/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):806-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Developmental Biology, Stanford University, Stanford, CA 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17975067" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Proliferation ; Diabetes, Gestational/*etiology/metabolism ; Female ; Humans ; Insulin/metabolism ; Insulin-Secreting Cells/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Obesity/metabolism ; Pregnancy ; Prolactin/metabolism ; Proto-Oncogene Proteins/*physiology ; Tumor Cells, Cultured
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  • 43
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-11-10
    Description: Prions are lethal mammalian pathogens composed of aggregated conformational isomers of a host-encoded glycoprotein and which appear to lack nucleic acids. Their unique biology, allied with the public-health risks posed by prion zoonoses such as bovine spongiform encephalopathy, has focused much attention on the molecular basis of prion propagation and the "species barrier" that controls cross-species transmission. Both are intimately linked to understanding how multiple prion "strains" are encoded by a protein-only agent. The underlying mechanisms are clearly of much wider importance, and analogous protein-based inheritance mechanisms are recognized in yeast and fungi. Recent advances suggest that prions themselves are not directly neurotoxic, but rather their propagation involves production of toxic species, which may be uncoupled from infectivity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Collinge, John -- Clarke, Anthony R -- MC_U123160656/Medical Research Council/United Kingdom -- MC_U123192748/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2007 Nov 9;318(5852):930-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK. j.collinge@prion.ucl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17991853" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Chemistry ; Humans ; Models, Biological ; PrPC Proteins/chemistry/isolation & purification/metabolism ; PrPSc Proteins/*chemistry/isolation & purification/metabolism/*pathogenicity ; Prion Diseases/*metabolism/*transmission ; Prions/*chemistry/isolation & purification/*pathogenicity ; Protein Conformation ; Protein Folding ; Recombinant Proteins/chemistry ; Species Specificity
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  • 44
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-11-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, Jennifer -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):729.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17975038" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diabetes, Gestational/*metabolism ; Female ; Humans ; Insulin-Secreting Cells/cytology ; Mice ; Pregnancy ; Prolactin/physiology ; Proto-Oncogene Proteins/genetics/*physiology ; Tumor Suppressor Proteins/*physiology
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  • 45
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-10-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Richard -- New York, N.Y. -- Science. 2007 Oct 19;318(5849):390; author reply 390.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17947563" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/*physiology ; Animals ; Glucuronidase/deficiency/*genetics ; Humans ; Mice ; *Models, Animal ; Signal Transduction ; Vitamin D/*administration & dosage/metabolism ; Wnt Proteins/metabolism
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  • 46
    Publication Date: 2007-11-17
    Description: Artificial biochemical circuits are likely to play as large a role in biological engineering as electrical circuits have played in the engineering of electromechanical devices. Toward that end, nucleic acids provide a designable substrate for the regulation of biochemical reactions. However, it has been difficult to incorporate signal amplification components. We introduce a design strategy that allows a specified input oligonucleotide to catalyze the release of a specified output oligonucleotide, which in turn can serve as a catalyst for other reactions. This reaction, which is driven forward by the configurational entropy of the released molecule, provides an amplifying circuit element that is simple, fast, modular, composable, and robust. We have constructed and characterized several circuits that amplify nucleic acid signals, including a feedforward cascade with quadratic kinetics and a positive feedback circuit with exponential growth kinetics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, David Yu -- Turberfield, Andrew J -- Yurke, Bernard -- Winfree, Erik -- New York, N.Y. -- Science. 2007 Nov 16;318(5853):1121-5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Computation and Neural Systems, California Institute of Technology, MC 136-93, 1200 East California Boulevard, Pasadena, CA91125, USA. dzhang@dna.caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18006742" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Catalysis ; Chemical Engineering ; *Computers, Molecular ; DNA/*chemistry ; Entropy ; Equipment Design ; Feedback, Physiological ; Mice ; Nanotechnology ; Nucleic Acid Hybridization ; Rabbits
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  • 47
    Publication Date: 2007-01-27
    Description: The normal synovium forms a membrane at the edges of joints and provides lubrication and nutrients for the cartilage. In rheumatoid arthritis, the synovium is the site of inflammation, and it participates in an organized tissue response that damages cartilage and bone. We identified cadherin-11 as essential for the development of the synovium. Cadherin-11-deficient mice have a hypoplastic synovial lining, display a disorganized synovial reaction to inflammation, and are resistant to inflammatory arthritis. Cadherin-11 therapeutics prevent and reduce arthritis in mouse models. Thus, synovial cadherin-11 determines the behavior of synovial cells in their proinflammatory and destructive tissue response in inflammatory arthritis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, David M -- Kiener, Hans P -- Agarwal, Sandeep K -- Noss, Erika H -- Watts, Gerald F M -- Chisaka, Osamu -- Takeichi, Masatoshi -- Brenner, Michael B -- K08 AR2214/AR/NIAMS NIH HHS/ -- R01 AR48114/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Feb 16;315(5814):1006-10. Epub 2007 Jan 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine and Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17255475" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies, Monoclonal/therapeutic use ; Arthritis, Experimental ; Arthritis, Rheumatoid/metabolism/*pathology/therapy ; Cadherins/*antagonists & inhibitors/biosynthesis/deficiency/*physiology ; Cell Adhesion/physiology ; Disease Models, Animal ; Extracellular Matrix/metabolism ; Fibroblasts/metabolism ; L Cells (Cell Line) ; Male ; Mice ; Mice, Inbred C57BL ; Organ Culture Techniques ; Synovial Membrane/*cytology/*pathology
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  • 48
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-11-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Miller, Greg -- New York, N.Y. -- Science. 2007 Nov 9;318(5852):899-900.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17991833" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Adult Stem Cells/chemistry/*cytology ; Animals ; Biomarkers/*analysis ; Brain/cytology/embryology ; Brain Chemistry ; Child ; Fatty Acids/analysis ; Hippocampus/chemistry/*cytology ; Humans ; Magnetic Resonance Spectroscopy/*methods ; Mice ; Rats ; Stem Cells/chemistry/*cytology
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  • 49
    Publication Date: 2007-07-21
    Description: PDZ domains have long been thought to cluster into discrete functional classes defined by their peptide-binding preferences. We used protein microarrays and quantitative fluorescence polarization to characterize the binding selectivity of 157 mouse PDZ domains with respect to 217 genome-encoded peptides. We then trained a multidomain selectivity model to predict PDZ domain-peptide interactions across the mouse proteome with an accuracy that exceeds many large-scale, experimental investigations of protein-protein interactions. Contrary to the current paradigm, PDZ domains do not fall into discrete classes; instead, they are evenly distributed throughout selectivity space, which suggests that they have been optimized across the proteome to minimize cross-reactivity. We predict that focusing on families of interaction domains, which facilitates the integration of experimentation and modeling, will play an increasingly important role in future investigations of protein function.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674608/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674608/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stiffler, Michael A -- Chen, Jiunn R -- Grantcharova, Viara P -- Lei, Ying -- Fuchs, Daniel -- Allen, John E -- Zaslavskaia, Lioudmila A -- MacBeath, Gavin -- 1 RO1 GM072872-01/GM/NIGMS NIH HHS/ -- 5 T32 GM07598-25/GM/NIGMS NIH HHS/ -- R01 GM072872/GM/NIGMS NIH HHS/ -- R01 GM072872-04/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 20;317(5836):364-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17641200" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Amino Acid Sequence ; Animals ; Computational Biology ; Computer Simulation ; Fluorescence Polarization ; Mice ; Peptides/*metabolism ; Protein Array Analysis ; Protein Binding ; *Protein Structure, Tertiary ; Proteome/chemistry/*metabolism
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  • 50
    Publication Date: 2007-02-03
    Description: Plasmacytoid dendritic cells (pDCs) detect viruses in the acidified endosomes by means of Toll-like receptors (TLRs). Yet, pDC responses to certain single-stranded RNA (ssRNA) viruses occur only after live viral infection. We present evidence here that the recognition of such viruses by TLR7 requires transport of cytosolic viral replication intermediates into the lysosome by the process of autophagy. In addition, autophagy was found to be required for the production of interferon-alpha by pDCs. These results support a key role for autophagy in mediating ssRNA virus detection and interferon-alpha secretion by pDCs and suggest that cytosolic replication intermediates of viruses serve as pathogen signatures recognized by TLR7.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Heung Kyu -- Lund, Jennifer M -- Ramanathan, Balaji -- Mizushima, Noboru -- Iwasaki, Akiko -- AI054359/AI/NIAID NIH HHS/ -- AI064705/AI/NIAID NIH HHS/ -- AI07019/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 9;315(5817):1398-401. Epub 2007 Feb 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272685" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Autophagy ; Dendritic Cells/*immunology/physiology/*virology ; Endosomes/immunology/virology ; Female ; Immunity, Innate ; Interferon-alpha/metabolism ; Interleukin-12/metabolism ; Lysosomes/virology ; Male ; Membrane Glycoproteins/*immunology ; Mice ; Mice, Transgenic ; Phagosomes/physiology/ultrastructure ; RNA, Viral/*immunology/metabolism ; Rhabdoviridae Infections/*immunology ; Toll-Like Receptor 7/*immunology ; Vesicular stomatitis Indiana virus/*immunology/physiology ; Virus Replication
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  • 51
    Publication Date: 2007-07-07
    Description: Inflammation is increasingly recognized as an important component of tumorigenesis, although the mechanisms and pathways involved are not well understood. Tumor development is regulated by products of several modifier genes, but instructions for their tumor-specific expression are currently unknown. We show that the signaling through the adaptor protein MyD88 has a critical role in spontaneous tumor development in mice with heterozygous mutation in the adenomatous polyposis coli (APC) gene. We found that MyD88-dependent signaling controls the expression of several key modifier genes of intestinal tumorigenesis and has a critical role in both spontaneous and carcinogen-induced tumor development. This study thus reveals the important role of an innate immune signaling pathway in intestinal tumorigenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rakoff-Nahoum, Seth -- Medzhitov, Ruslan -- New York, N.Y. -- Science. 2007 Jul 6;317(5834):124-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17615359" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Cell Proliferation ; Colonic Neoplasms/genetics/immunology/pathology/physiopathology ; Disease Models, Animal ; Female ; Gene Expression Regulation, Neoplastic ; Genes, APC ; Immunity, Innate ; Intestinal Neoplasms/genetics/immunology/pathology/*physiopathology ; Intestine, Large/pathology ; Intestine, Small/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Myeloid Differentiation Factor 88/genetics/*physiology ; *Signal Transduction
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  • 52
    Publication Date: 2007-01-06
    Description: Endoplasmic reticulum-localized protein-tyrosine phosphatase PTP1B terminates growth factor signal transduction by dephosphorylation of receptor tyrosine kinases (RTKs). But how PTP1B allows for RTK signaling in the cytoplasm is unclear. In order to test whether PTP1B activity is spatially regulated, we developed a method based on Forster resonant energy transfer for imaging enzyme-substrate (ES) intermediates in live cells. We observed the establishment of a steady-state ES gradient across the cell. This gradient exhibited robustness to cell-to-cell variability, growth factor activation, and RTK localization, which demonstrated spatial regulation of PTP1B activity. Such regulation may be important for generating distinct cellular environments that permit RTK signal transduction and that mediate its eventual termination.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yudushkin, Ivan A -- Schleifenbaum, Andreas -- Kinkhabwala, Ali -- Neel, Benjamin G -- Schultz, Carsten -- Bastiaens, Philippe I H -- R01 DK60838/DK/NIDDK NIH HHS/ -- R37 49152/PHS HHS/ -- New York, N.Y. -- Science. 2007 Jan 5;315(5808):115-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, D-69117 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17204654" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; COS Cells ; Catalysis ; Cell Line, Tumor ; Cercopithecus aethiops ; Epidermal Growth Factor/metabolism/pharmacology ; Fluorescence Resonance Energy Transfer ; Humans ; Kinetics ; Mathematics ; Microscopy, Fluorescence ; Models, Biological ; Phosphorylation ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; Protein Tyrosine Phosphatases/*metabolism ; Receptor Protein-Tyrosine Kinases/*metabolism ; Receptor, Epidermal Growth Factor/*metabolism ; Recombinant Fusion Proteins/metabolism
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  • 53
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-03-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reis e Sousa, Caetano -- New York, N.Y. -- Science. 2007 Mar 9;315(5817):1376-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. caetano@cancer.org.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17347432" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Autophagy ; Cytokines/metabolism ; Dendritic Cells/*immunology/physiology/*virology ; Endosomes/immunology/virology ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class II/immunology ; Membrane Glycoproteins/immunology/physiology ; Mice ; Mice, Transgenic ; RNA, Viral/*immunology/metabolism ; Rhabdoviridae Infections/*immunology ; Signal Transduction ; Toll-Like Receptor 7/immunology/physiology ; Toll-Like Receptor 9/immunology/physiology ; Toll-Like Receptors/immunology/*physiology ; Vesicular stomatitis Indiana virus/*immunology/physiology ; Virus Replication
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  • 54
    Publication Date: 2007-05-19
    Description: Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kapranov, Philipp -- Cheng, Jill -- Dike, Sujit -- Nix, David A -- Duttagupta, Radharani -- Willingham, Aarron T -- Stadler, Peter F -- Hertel, Jana -- Hackermuller, Jorg -- Hofacker, Ivo L -- Bell, Ian -- Cheung, Evelyn -- Drenkow, Jorg -- Dumais, Erica -- Patel, Sandeep -- Helt, Gregg -- Ganesh, Madhavan -- Ghosh, Srinka -- Piccolboni, Antonio -- Sementchenko, Victor -- Tammana, Hari -- Gingeras, Thomas R -- N01-CO-12400/CO/NCI NIH HHS/ -- U01HG003147/HG/NHGRI NIH HHS/ -- New York, N.Y. -- Science. 2007 Jun 8;316(5830):1484-8. Epub 2007 May 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Affymetrix Laboratory, Affymetrix, Inc., 3420 Central Expressway, Santa Clara, CA, 95051, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17510325" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cytosol/metabolism ; Exons ; Gene Expression ; Genome ; *Genome, Human ; HeLa Cells ; Humans ; Mice ; Promoter Regions, Genetic ; RNA/*genetics/metabolism ; RNA Precursors/*genetics/metabolism ; RNA, Messenger/*genetics/*metabolism ; Synteny ; Terminator Regions, Genetic ; *Transcription, Genetic
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  • 55
    Publication Date: 2007-05-05
    Description: We found that, in the mouse visual cortex, action potentials generated in a single layer-2/3 pyramidal (excitatory) neuron can reliably evoke large, constant-latency inhibitory postsynaptic currents in other nearby pyramidal cells. This effect is mediated by axo-axonic ionotropic glutamate receptor-mediated excitation of the nerve terminals of inhibitory interneurons, which connect to the target pyramidal cells. Therefore, individual cortical excitatory neurons can generate inhibition independently from the somatic firing of inhibitory interneurons.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ren, Ming -- Yoshimura, Yumiko -- Takada, Naoki -- Horibe, Shoko -- Komatsu, Yukio -- New York, N.Y. -- Science. 2007 May 4;316(5825):758-61.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Neuroscience, Research Institute of Environmental Medicine, Nagoya University, Nagoya 464-8601, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17478724" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials ; Animals ; Axons/metabolism ; Electric Stimulation ; Excitatory Postsynaptic Potentials ; Glutamic Acid/metabolism/pharmacology ; *Inhibitory Postsynaptic Potentials ; Interneurons/physiology ; Mice ; Mice, Inbred C57BL ; Neural Inhibition ; Patch-Clamp Techniques ; Presynaptic Terminals/physiology ; Pyramidal Cells/*physiology ; Receptors, AMPA/physiology ; Receptors, Kainic Acid/physiology ; Synapses/*physiology ; Synaptic Transmission ; Visual Cortex/cytology/*physiology ; gamma-Aminobutyric Acid/metabolism
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  • 56
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-02-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kearns, Daniel B -- New York, N.Y. -- Science. 2007 Feb 9;315(5813):773-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, Indiana University, Bloomington, IN 47405, USA. dbkearns@indiana.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17289965" target="_blank"〉PubMed〈/a〉
    Keywords: *Bacterial Adhesion ; Bacterial Proteins/genetics/*physiology ; Fimbriae, Bacterial/physiology ; Focal Adhesions/*physiology ; Models, Biological ; Molecular Motor Proteins/genetics/*physiology ; Movement ; Myxococcus xanthus/*physiology
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  • 57
    Publication Date: 2007-04-28
    Description: By screening N-ethyl-N-nitrosourea-mutagenized animals for alterations in rhythms of wheel-running activity, we identified a mouse mutation, after hours (Afh). The mutation, a Cys(358)Ser substitution in Fbxl3, an F-box protein with leucine-rich repeats, results in long free-running rhythms of about 27 hours in homozygotes. Circadian transcriptional and translational oscillations are attenuated in Afh mice. The Afh allele significantly affected Per2 expression and delayed the rate of Cry protein degradation in Per2::Luciferase tissue slices. Our in vivo and in vitro studies reveal a central role for Fbxl3 in mammalian circadian timekeeping.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Godinho, Sofia I H -- Maywood, Elizabeth S -- Shaw, Linda -- Tucci, Valter -- Barnard, Alun R -- Busino, Luca -- Pagano, Michele -- Kendall, Rachel -- Quwailid, Mohamed M -- Romero, M Rosario -- O'neill, John -- Chesham, Johanna E -- Brooker, Debra -- Lalanne, Zuzanna -- Hastings, Michael H -- Nolan, Patrick M -- MC_U105170643/Medical Research Council/United Kingdom -- MC_U142684172/Medical Research Council/United Kingdom -- MC_U142684173/Medical Research Council/United Kingdom -- MC_U142684175/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2007 May 11;316(5826):897-900. Epub 2007 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council (MRC) Mammalian Genetics Unit, Harwell, Oxfordshire OX11 0RD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463252" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; CLOCK Proteins ; COS Cells ; Cell Cycle Proteins/genetics/metabolism ; Cercopithecus aethiops ; *Circadian Rhythm/genetics ; Crosses, Genetic ; Cryptochromes ; F-Box Proteins/*genetics/*physiology ; Female ; Flavoproteins/genetics/metabolism ; Gene Expression Regulation ; Liver/metabolism ; Lung/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Molecular Sequence Data ; Nuclear Proteins/genetics/metabolism ; Period Circadian Proteins ; *Point Mutation ; Suprachiasmatic Nucleus/metabolism ; Trans-Activators/genetics/metabolism ; Transcription Factors/genetics/metabolism ; Transcription, Genetic
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  • 58
    Publication Date: 2007-02-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Couzin, Jennifer -- New York, N.Y. -- Science. 2007 Feb 2;315(5812):587.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272695" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Genetic Engineering ; Homeodomain Proteins/genetics/physiology ; Liver/cytology/*embryology ; Mice ; Organ Size ; Pancreas/cytology/*embryology ; Stem Cells/*physiology ; Trans-Activators/genetics/physiology
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  • 59
    Publication Date: 2007-04-21
    Description: Competition between neurons is necessary for refining neural circuits during development and may be important for selecting the neurons that participate in encoding memories in the adult brain. To examine neuronal competition during memory formation, we conducted experiments with mice in which we manipulated the function of CREB (adenosine 3',5'-monophosphate response element-binding protein) in subsets of neurons. Changes in CREB function influenced the probability that individual lateral amygdala neurons were recruited into a fear memory trace. Our results suggest a competitive model underlying memory formation, in which eligible neurons are selected to participate in amemorytrace as a function of their relative CREB activity at the time of learning.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Han, Jin-Hee -- Kushner, Steven A -- Yiu, Adelaide P -- Cole, Christy J -- Matynia, Anna -- Brown, Robert A -- Neve, Rachael L -- Guzowski, John F -- Silva, Alcino J -- Josselyn, Sheena A -- AG13622/AG/NIA NIH HHS/ -- P01HD33098/HD/NICHD NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 20;316(5823):457-60.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Neurosciences and Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17446403" target="_blank"〉PubMed〈/a〉
    Keywords: Amygdala/*physiology ; Animals ; Conditioning (Psychology) ; Cyclic AMP Response Element-Binding Protein/genetics/*metabolism ; Cytoskeletal Proteins/genetics/metabolism ; Fear ; Genetic Vectors ; Memory/*physiology ; Mice ; Nerve Tissue Proteins/genetics/metabolism ; Neuronal Plasticity ; Neurons/metabolism/*physiology ; Transcription, Genetic
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  • 60
    Publication Date: 2007-10-06
    Description: The simple circadian oscillator found in cyanobacteria can be reconstituted in vitro using three proteins-KaiA, KaiB, and KaiC. The total phosphorylation level of KaiC oscillates with a circadian period, but the mechanism underlying its sustained oscillation remains unclear. We have shown that four forms of KaiC differing in their phosphorylation state appear in an ordered pattern arising from the intrinsic autokinase and autophosphatase rates of KaiC and their modulation by KaiA. Kinetic and biochemical data indicate that one of these phosphoforms inhibits the activity of KaiA through interaction with KaiB, providing the crucial feedback that sustains oscillation. A mathematical model constrained by experimental data quantitatively reproduces the circadian period and the distinctive dynamics of the four phosphoforms.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427396/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2427396/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rust, Michael J -- Markson, Joseph S -- Lane, William S -- Fisher, Daniel S -- O'Shea, Erin K -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):809-12. Epub 2007 Oct 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Faculty of Arts and Sciences Center for Systems Biology, Departments of Molecular and Cellular Biology and of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17916691" target="_blank"〉PubMed〈/a〉
    Keywords: Bacterial Proteins/*physiology ; Biological Clocks/*physiology ; Circadian Rhythm/*physiology ; Circadian Rhythm Signaling Peptides and Proteins ; Models, Biological ; Phosphorylation ; Synechococcus/*physiology
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  • 61
    Publication Date: 2007-03-03
    Description: IKKepsilon is an IKK (inhibitor of nuclear factor kappaBkinase)-related kinase implicated in virus induction of interferon-beta (IFNbeta). We report that, although mice lacking IKKepsilon produce normal amounts of IFNbeta, they are hypersusceptible to viral infection because of a defect in the IFN signaling pathway. Specifically, a subset of type I IFN-stimulated genes are not activated in the absence of IKKepsilon because the interferon-stimulated gene factor 3 complex (ISGF3) does not bind to promoter elements of the affected genes. We demonstrate that IKKepsilon is activated by IFNbeta and that IKKepsilon directly phosphorylates signal transducer and activator of transcription 1 (STAT1), a component of ISGF3. We conclude that IKKepsilon plays a critical role in the IFN-inducible antiviral transcriptional response.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tenoever, Benjamin R -- Ng, Sze-Ling -- Chua, Mark A -- McWhirter, Sarah M -- Garcia-Sastre, Adolfo -- Maniatis, Tom -- F31 AI056678/AI/NIAID NIH HHS/ -- P01AI058113/AI/NIAID NIH HHS/ -- R01AI46954/AI/NIAID NIH HHS/ -- U19AI62623/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 2;315(5816):1274-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17332413" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Deaminase/genetics/metabolism ; Animals ; Cells, Cultured ; Dimerization ; *Gene Expression Regulation ; I-kappa B Kinase/genetics/*metabolism ; *Influenza A Virus, H1N1 Subtype/immunology/physiology ; Interferon-Stimulated Gene Factor 3/metabolism ; Interferon-beta/*immunology/metabolism ; Lung/pathology/virology ; Mice ; Mice, Knockout ; Orthomyxoviridae Infections/*immunology/metabolism/pathology/virology ; Phosphorylation ; Promoter Regions, Genetic ; RNA-Binding Proteins ; STAT1 Transcription Factor/metabolism ; STAT2 Transcription Factor/metabolism ; Signal Transduction ; Transcription, Genetic ; Viral Load ; Virus Replication
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  • 62
    Publication Date: 2007-12-08
    Description: It has recently been demonstrated that mouse and human fibroblasts can be reprogrammed into an embryonic stem cell-like state by introducing combinations of four transcription factors. However, the therapeutic potential of such induced pluripotent stem (iPS) cells remained undefined. By using a humanized sickle cell anemia mouse model, we show that mice can be rescued after transplantation with hematopoietic progenitors obtained in vitro from autologous iPS cells. This was achieved after correction of the human sickle hemoglobin allele by gene-specific targeting. Our results provide proof of principle for using transcription factor-induced reprogramming combined with gene and cell therapy for disease treatment in mice. The problems associated with using retroviruses and oncogenes for reprogramming need to be resolved before iPS cells can be considered for human therapy.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hanna, Jacob -- Wernig, Marius -- Markoulaki, Styliani -- Sun, Chiao-Wang -- Meissner, Alexander -- Cassady, John P -- Beard, Caroline -- Brambrink, Tobias -- Wu, Li-Chen -- Townes, Tim M -- Jaenisch, Rudolf -- 2-R01-HL057619/HL/NHLBI NIH HHS/ -- 5-R37-CA084198/CA/NCI NIH HHS/ -- 5-RO1-CA087869/CA/NCI NIH HHS/ -- 5-RO1-HDO45022/PHS HHS/ -- New York, N.Y. -- Science. 2007 Dec 21;318(5858):1920-3. Epub 2007 Dec 6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18063756" target="_blank"〉PubMed〈/a〉
    Keywords: Anemia, Sickle Cell/blood/physiopathology/*therapy ; Animals ; Cell Differentiation ; Cells, Cultured ; *Cellular Reprogramming ; DNA-Binding Proteins/genetics ; Disease Models, Animal ; Embryonic Stem Cells/cytology ; Erythrocyte Count ; Fibroblasts/*cytology ; Genes, myc ; Globins/genetics ; Hematopoiesis ; *Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*cytology ; Hemoglobin A/analysis ; Hemoglobin, Sickle/analysis ; Humans ; Kidney Concentrating Ability ; Kruppel-Like Transcription Factors/genetics ; Male ; Mice ; Octamer Transcription Factor-3/genetics ; Pluripotent Stem Cells/*cytology ; SOXB1 Transcription Factors ; Trans-Activators/genetics ; Transduction, Genetic
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  • 63
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-09-22
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉DiNardo, Steve -- Braun, Robert E -- New York, N.Y. -- Science. 2007 Sep 21;317(5845):1696-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104-6058, USA. sdinardo@mail.med.upenn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17885122" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Male ; Mice ; Pluripotent Stem Cells/cytology ; Spermatogonia/*cytology ; Testis/*cytology
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  • 64
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansson, Goran K -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):206-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine and Center for Molecular Medicine, Karolinska Institute, Stockholm, SE-17176, Sweden. goran.hansson@ki.se〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431157" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Dendritic Cells/physiology ; Humans ; Lipase/metabolism ; Lipids/*blood ; Liver/enzymology/*physiology ; Lymphotoxin beta Receptor/metabolism ; Lymphotoxin-alpha/*physiology ; Mice ; T-Lymphocytes/physiology ; Tumor Necrosis Factor Ligand Superfamily Member 14/*physiology
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  • 65
    Publication Date: 2007-07-14
    Description: The temporal and spatial regulation of gene expression in mammalian development is linked to the establishment of functional chromatin domains. Here, we report that tissue-specific transcription of a retrotransposon repeat in the murine growth hormone locus is required for gene activation. This repeat serves as a boundary to block the influence of repressive chromatin modifications. The repeat element is able to generate short, overlapping Pol II-and Pol III-driven transcripts, both of which are necessary and sufficient to enable a restructuring of the regulated locus into nuclear compartments. These data suggest that transcription of interspersed repetitive sequences may represent a developmental strategy for the establishment of functionally distinct domains within the mammalian genome to control gene activation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lunyak, Victoria V -- Prefontaine, Gratien G -- Nunez, Esperanza -- Cramer, Thorsten -- Ju, Bong-Gun -- Ohgi, Kenneth A -- Hutt, Kasey -- Roy, Rosa -- Garcia-Diaz, Angel -- Zhu, Xiaoyan -- Yung, Yun -- Montoliu, Lluis -- Glass, Christopher K -- Rosenfeld, Michael G -- New York, N.Y. -- Science. 2007 Jul 13;317(5835):248-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, School of Medicine, University of California, San Diego, 9500 Gilman Drive, Room 345, La Jolla, CA 92093-0648, USA. vlunyak@uscd.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17626886" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Chromatin Immunoprecipitation ; DNA Polymerase II/metabolism ; DNA Polymerase III/metabolism ; *Gene Expression Regulation, Developmental ; Growth Hormone/*genetics ; Histones/metabolism ; *Insulator Elements ; Methylation ; Mice ; Mice, Transgenic ; Molecular Sequence Data ; *Organogenesis ; Pituitary Gland/*embryology/metabolism ; *Short Interspersed Nucleotide Elements ; *Transcription, Genetic ; Transcriptional Activation
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  • 66
    Publication Date: 2007-07-07
    Description: Hepatocellular carcinoma (HCC), the most common liver cancer, occurs mainly in men. Similar gender disparity is seen in mice given a chemical carcinogen, diethylnitrosamine (DEN). DEN administration caused greater increases in serum interleukin-6 (IL-6) concentration in males than it did in females. Furthermore, ablation of IL-6 abolished the gender differences in hepatocarcinogenesis in mice. DEN exposure promoted production of IL-6 in Kupffer cells (KCs) in a manner dependent on the Toll-like receptor adaptor protein MyD88, ablation of which also protected male mice from DEN-induced hepatocarcinogenesis. Estrogen inhibited secretion of IL-6 from KCs exposed to necrotic hepatocytes and reduced circulating concentrations of IL-6 in DEN-treated male mice. We propose that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Naugler, Willscott E -- Sakurai, Toshiharu -- Kim, Sunhwa -- Maeda, Shin -- Kim, Kyounghyun -- Elsharkawy, Ahmed M -- Karin, Michael -- CA118165/CA/NCI NIH HHS/ -- DK007202/DK/NIDDK NIH HHS/ -- ES004151/ES/NIEHS NIH HHS/ -- ES006376/ES/NIEHS NIH HHS/ -- R01 CA118165/CA/NCI NIH HHS/ -- R01 ES006376/ES/NIEHS NIH HHS/ -- T32 CA121938/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 6;317(5834):121-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, University of California, San Diego, CA 93093, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17615358" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carbon Tetrachloride/administration & dosage ; Diethylnitrosamine/administration & dosage/metabolism ; Estradiol/pharmacology ; Female ; Hepatocytes ; Interleukin-6/blood/genetics/*metabolism ; Kupffer Cells/*metabolism ; Liver/metabolism/pathology ; Liver Neoplasms, Experimental/chemically induced/immunology/*physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Differentiation Factor 88/*physiology ; Necrosis ; Ovariectomy ; RNA, Messenger/genetics/metabolism ; *Sex Characteristics
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  • 67
    Publication Date: 2007-02-10
    Description: Rett syndrome is an autism spectrum disorder caused by mosaic expression of mutant copies of the X-linked MECP2 gene in neurons. However, neurons do not die, which suggests that this is not a neurodegenerative disorder. An important question for future therapeutic approaches to this and related disorders concerns phenotypic reversibility. Can viable but defective neurons be repaired, or is the damage done during development without normal MeCP2 irrevocable? Using a mouse model, we demonstrate robust phenotypic reversal, as activation of MeCP2 expression leads to striking loss of advanced neurological symptoms in both immature and mature adult animals.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Guy, Jacky -- Gan, Jian -- Selfridge, Jim -- Cobb, Stuart -- Bird, Adrian -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2007 Feb 23;315(5815):1143-7. Epub 2007 Feb 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Centre for Cell Biology, Edinburgh University, King's Buildings, Edinburgh EH9 3JR, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17289941" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/metabolism ; Chimera ; Disease Models, Animal ; Female ; *Gene Expression Regulation ; Gene Targeting ; Long-Term Potentiation ; Male ; Methyl-CpG-Binding Protein 2/*genetics/metabolism ; Mice ; Mice, Inbred C57BL ; Neurons/*physiology ; Phenotype ; Rett Syndrome/*genetics/physiopathology/*therapy ; Synaptic Transmission ; Tamoxifen/pharmacology ; Transgenes
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  • 68
    Publication Date: 2007-04-28
    Description: MicroRNAs are small RNA species involved in biological control at multiple levels. Using genetic deletion and transgenic approaches, we show that the evolutionarily conserved microRNA-155 (miR-155) has an important role in the mammalian immune system, specifically in regulating T helper cell differentiation and the germinal center reaction to produce an optimal T cell-dependent antibody response. miR-155 exerts this control, at least in part, by regulating cytokine production. These results also suggest that individual microRNAs can exert critical control over mammalian differentiation processes in vivo.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Thai, To-Ha -- Calado, Dinis Pedro -- Casola, Stefano -- Ansel, K Mark -- Xiao, Changchun -- Xue, Yingzi -- Murphy, Andrew -- Frendewey, David -- Valenzuela, David -- Kutok, Jeffery L -- Schmidt-Supprian, Marc -- Rajewsky, Nikolaus -- Yancopoulos, George -- Rao, Anjana -- Rajewsky, Klaus -- AI064345/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Apr 27;316(5824):604-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463289" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*immunology ; Cell Differentiation ; Cells, Cultured ; Cytokines/biosynthesis ; Germinal Center/*immunology ; Immunoglobulin G/analysis ; Lymphocyte Activation ; Lymphotoxin-alpha/biosynthesis ; Lymphotoxin-beta/biosynthesis ; Mice ; Mice, Knockout ; Mice, Transgenic ; MicroRNAs/genetics/*physiology ; Nitrophenols/immunology ; Peyer's Patches/immunology ; Phenylacetates ; Somatic Hypermutation, Immunoglobulin ; Spleen/immunology ; T-Lymphocytes/cytology/*immunology/metabolism ; Th1 Cells/cytology/immunology ; Th2 Cells/cytology/immunology ; Tumor Necrosis Factor-alpha/biosynthesis
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  • 69
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-02-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hajnoczky, Gyorgy -- Hoek, Jan B -- New York, N.Y. -- Science. 2007 Feb 2;315(5812):607-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA. gyorgy.hajnoczky@jefferson.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17272709" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/*metabolism ; Animals ; *Apoptosis ; Autophagy ; Calcium Signaling ; *Cell Aging ; Cytoplasm/metabolism ; Hydrogen Peroxide/metabolism/pharmacology ; Intracellular Membranes/metabolism ; Mice ; Mitochondria/*metabolism ; Models, Biological ; Peptidylprolyl Isomerase/metabolism ; Permeability ; Phosphorylation ; Protein Kinase C/metabolism ; Protein Kinase C beta ; Protein Transport ; Reactive Oxygen Species/metabolism ; Shc Signaling Adaptor Proteins ; *Signal Transduction
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  • 70
    Publication Date: 2007-07-14
    Description: Changes in protein-protein interactions may allow polypeptides to perform unexpected regulatory functions. Mammalian ShcA docking proteins have amino-terminal phosphotyrosine (pTyr) binding (PTB) and carboxyl-terminal Src homology 2 (SH2) domains, which recognize specific pTyr sites on activated receptors, and a central region with two phosphorylated tyrosine-X-asparagine (pYXN) motifs (where X represents any amino acid) that each bind the growth factor receptor-bound protein 2 (Grb2) adaptor. Phylogenetic analysis indicates that ShcA may signal through both pYXN-dependent and -independent pathways. We show that, in mice, cardiomyocyte-expressed ShcA directs mid-gestational heart development by a PTB-dependent mechanism that does not require the pYXN motifs. In contrast, the pYXN motifs are required with PTB and SH2 domains in the same ShcA molecule for the formation of muscle spindles, skeletal muscle sensory organs that regulate motor behavior. Thus, combinatorial differences in ShcA docking interactions may yield multiple signaling mechanisms to support diversity in tissue morphogenesis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575375/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2575375/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hardy, W Rod -- Li, Lingying -- Wang, Zhi -- Sedy, Jiri -- Fawcett, James -- Frank, Eric -- Kucera, Jan -- Pawson, Tony -- R01 NS024373/NS/NINDS NIH HHS/ -- R01 NS024373-18/NS/NINDS NIH HHS/ -- R01 NS024373-19/NS/NINDS NIH HHS/ -- R01 NS024373-20/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2007 Jul 13;317(5835):251-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17626887" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/chemistry/genetics/*metabolism ; Amino Acid Motifs ; Animals ; Ataxia ; Excitatory Postsynaptic Potentials ; Genetic Complementation Test ; Heart/*embryology ; Mice ; Mice, Knockout ; *Morphogenesis ; Motor Activity ; Muscle Spindles/*embryology ; Muscle, Skeletal/*embryology/metabolism ; Mutation ; Myocytes, Cardiac/*metabolism ; Neurons, Afferent/physiology ; Phosphorylation ; Protein Structure, Tertiary ; Shc Signaling Adaptor Proteins ; Signal Transduction ; src Homology Domains
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  • 71
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-08-04
    Description: Much progress has been made in understanding how the immune system is regulated, with a great deal of recent interest in naturally occurring CD4+ regulatory T cells that actively engage in the maintenance of immunological self-tolerance and immune homeostasis. The challenge ahead for immunologists is the further elucidation of the molecular and cellular processes that govern the development and function of these cells. From this, exciting possibilities are emerging for the manipulation of regulatory T cell pathways in treating immunological diseases and suppressing or augmenting physiological immune responses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sakaguchi, Shimon -- Powrie, Fiona -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):627-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17673654" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/immunology ; Antigens/immunology ; Autoimmune Diseases/immunology ; Forkhead Transcription Factors/metabolism ; Homeostasis ; Humans ; Immune Tolerance ; Infection/immunology ; Inflammation/immunology ; Lymphocyte Activation ; Mice ; Self Tolerance ; T-Lymphocytes/immunology ; T-Lymphocytes, Regulatory/*immunology/physiology
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  • 72
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-04-21
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dolan, Liam -- New York, N.Y. -- Science. 2007 Apr 20;316(5823):377-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cell and Developmental Biology, John Innes Centre, Norwich NR4 7UH, UK. liam.dolan@bbsrc.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17446377" target="_blank"〉PubMed〈/a〉
    Keywords: Arabidopsis/cytology/genetics/growth & development/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Biological Evolution ; Cell Nucleus/metabolism ; Feedback, Physiological ; Genetic Engineering ; Models, Biological ; Plant Cells ; Plant Development ; Plant Roots/cytology/growth & development/*metabolism ; Plants/genetics/metabolism ; Protein Transport ; Transcription Factors/genetics/*metabolism
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 73
    Publication Date: 2007-04-28
    Description: One component of the circadian clock in mammals is the Clock-Bmal1 heterodimeric transcription factor. Among its downstream targets, two genes, Cry1 and Cry2, encode inhibitors of the Clock-Bmal1 complex that establish a negative-feedback loop. We found that both Cry1 and Cry2 proteins are ubiquitinated and degraded via the SCF(Fbxl3) ubiquitin ligase complex. This regulation by SCF(Fbxl3) is a prerequisite for the efficient and timely reactivation of Clock-Bmal1 and the consequent expression of Per1 and Per2, two regulators of the circadian clock that display tumor suppressor activity. Silencing of Fbxl3 produced no effect in Cry1-/-;Cry2-/- cells, which shows that Fbxl3 controls clock oscillations by mediating the degradation of CRY proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Busino, Luca -- Bassermann, Florian -- Maiolica, Alessio -- Lee, Choogon -- Nolan, Patrick M -- Godinho, Sofia I H -- Draetta, Giulio F -- Pagano, Michele -- MC_U142684172/Medical Research Council/United Kingdom -- MC_U142684173/Medical Research Council/United Kingdom -- MC_U142684175/Medical Research Council/United Kingdom -- R01-GM57587/GM/NIGMS NIH HHS/ -- R21-CA125173/CA/NCI NIH HHS/ -- R37-CA76584/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 May 11;316(5826):900-4. Epub 2007 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, MSB 599, New York, NY 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17463251" target="_blank"〉PubMed〈/a〉
    Keywords: ARNTL Transcription Factors ; Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; CLOCK Proteins ; Cell Cycle Proteins/genetics/metabolism ; Cells, Cultured ; *Circadian Rhythm/genetics ; Cryptochromes ; F-Box Proteins/genetics/*metabolism ; Flavoproteins/genetics/*metabolism ; HeLa Cells ; Humans ; Mice ; NIH 3T3 Cells ; Nuclear Proteins/genetics/metabolism ; Period Circadian Proteins ; Promoter Regions, Genetic ; RNA Interference ; SKP Cullin F-Box Protein Ligases/*metabolism ; Trans-Activators/metabolism ; Transcription Factors/genetics/metabolism ; Transfection ; Ubiquitin/metabolism
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  • 74
    Publication Date: 2007-04-21
    Description: Nearly half of the mammalian genome is composed of repeated sequences. In Drosophila, Piwi proteins exert control over transposons. However, mammalian Piwi proteins, MIWI and MILI, partner with Piwi-interacting RNAs (piRNAs) that are depleted of repeat sequences, which raises questions about a role for mammalian Piwi's in transposon control. A search for murine small RNAs that might program Piwi proteins for transposon suppression revealed developmentally regulated piRNA loci, some of which resemble transposon master control loci of Drosophila. We also find evidence of an adaptive amplification loop in which MILI catalyzes the formation of piRNA 5' ends. Mili mutants derepress LINE-1 (L1) and intracisternal A particle and lose DNA methylation of L1 elements, demonstrating an evolutionarily conserved role for PIWI proteins in transposon suppression.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Aravin, Alexei A -- Sachidanandam, Ravi -- Girard, Angelique -- Fejes-Toth, Katalin -- Hannon, Gregory J -- New York, N.Y. -- Science. 2007 May 4;316(5825):744-7. Epub 2007 Apr 19.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Watson School of Biological Sciences, Cold Spring Harbor Laboratory, Howard Hughes Medical Institute (HHMI), 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17446352" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions ; Animals ; Argonaute Proteins ; Cluster Analysis ; Computational Biology ; DNA Methylation ; Genes, Intracisternal A-Particle ; Long Interspersed Nucleotide Elements ; Male ; Meiosis ; Mice ; Mutation ; Proteins/*metabolism ; RNA, Antisense/genetics/metabolism ; RNA, Untranslated/*genetics/metabolism ; *Retroelements ; Reverse Transcriptase Polymerase Chain Reaction ; Short Interspersed Nucleotide Elements ; Spermatocytes/cytology/*metabolism ; Spermatogenesis ; *Suppression, Genetic
    Print ISSN: 0036-8075
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  • 75
    Publication Date: 2007-10-06
    Description: Mounting a protective immune response is critically dependent on the orchestrated movement of cells within lymphoid organs. We report here the visualization, using major histocompatability complex class I tetramers, of the CD8-positive (CD8) T cell response in the spleens of mice to Listeria monocytogenes infection. A multistage pathway was revealed that included initial activation at the borders of the B and T cell zones followed by cluster formation with antigenpresenting cells leading to CD8 T cell exit to the red pulp via bridging channels. Strikingly, many memory CD8 T cells localized to the B cell zones and, when challenged, underwent rapid migration to the T cell zones where proliferation occurred, followed by egress via bridging channels in parallel with the primary response. Thus, the ability to track endogenous immune responses has uncovered both distinct and overlapping mechanisms and anatomical locations driving primary and secondary immune responses.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846662/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2846662/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khanna, Kamal M -- McNamara, Jeffery T -- Lefrancois, Leo -- AI41576/AI/NIAID NIH HHS/ -- AI56172/AI/NIAID NIH HHS/ -- DRG-1886-05/PHS HHS/ -- P01 AI056172/AI/NIAID NIH HHS/ -- P01 AI056172-05/AI/NIAID NIH HHS/ -- R01 AI041576/AI/NIAID NIH HHS/ -- R01 AI041576-06/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Oct 5;318(5847):116-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, University of Connecticut, Farmington, CT 06030, U.S.A.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17916739" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigen-Presenting Cells/immunology ; Antigens, CD/analysis ; Antigens, CD8/analysis ; B-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/cytology/*immunology/physiology ; Cell Movement ; Dendritic Cells/immunology/physiology ; Fluorescent Dyes ; Histocompatibility Antigens Class I ; *Immunologic Memory ; Kinetics ; Listeria monocytogenes/*immunology ; Listeriosis/*immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal ; Receptors, Antigen, T-Cell/analysis ; Spleen/cytology/*immunology ; Staining and Labeling ; T-Lymphocyte Subsets/cytology/immunology/physiology
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 76
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-01-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oldroyd, Giles E D -- New York, N.Y. -- Science. 2007 Jan 5;315(5808):52-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Disease and Stress Biology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK. giles.oldroyd@bbsrc.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17204633" target="_blank"〉PubMed〈/a〉
    Keywords: Calcium/metabolism ; Calcium-Calmodulin-Dependent Protein Kinases/genetics/metabolism ; Cytokinins/*metabolism ; Lipopolysaccharides/metabolism ; Lotus/cytology/metabolism/*microbiology/*physiology ; Models, Biological ; Mutation ; Nitrogen Fixation ; Plant Epidermis/cytology/metabolism ; Plant Roots/cytology/microbiology ; Protein Kinases/genetics/*metabolism ; Receptors, Cell Surface/genetics/metabolism ; Rhizobiaceae/physiology ; Root Nodules, Plant/cytology/*growth & development/microbiology ; *Signal Transduction ; Symbiosis ; Transcription Factors/metabolism
    Print ISSN: 0036-8075
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  • 77
    Publication Date: 2007-04-07
    Description: Kinesin-1 is a two-headed molecular motor that walks along microtubules, with each step gated by adenosine triphosphate (ATP) binding. Existing models for the gating mechanism propose a role for the microtubule lattice. We show that unpolymerized tubulin binds to kinesin-1, causing tubulin-activated release of adenosine diphosphate (ADP). With no added nucleotide, each kinesin-1 dimer binds one tubulin heterodimer. In adenylyl-imidodiphosphate (AMP-PNP), a nonhydrolyzable ATP analog, each kinesin-1 dimer binds two tubulin heterodimers. The data reveal an ATP gate that operates independently of the microtubule lattice, by ATP-dependent release of a steric or allosteric block on the tubulin binding site of the tethered kinesin-ADP head.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504013/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2504013/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alonso, Maria C -- Drummond, Douglas R -- Kain, Susan -- Hoeng, Julia -- Amos, Linda -- Cross, Robert A -- G0200542/Medical Research Council/United Kingdom -- G0200542(63814)/Medical Research Council/United Kingdom -- MC_U105184313/Medical Research Council/United Kingdom -- U.1051.04.002(78842)/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2007 Apr 6;316(5821):120-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Motors Group, Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17412962" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/*metabolism ; Adenylyl Imidodiphosphate/metabolism ; Animals ; Binding Sites ; Dimerization ; Kinesin/chemistry/*metabolism ; Microtubules/*metabolism ; Models, Biological ; Molecular Motor Proteins/*metabolism ; Neurospora ; Protein Conformation ; Rats ; Recombinant Fusion Proteins/chemistry/metabolism ; Schizosaccharomyces ; Tubulin/chemistry/*metabolism
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  • 78
    Publication Date: 2007-03-03
    Description: A hallmark of mammalian immunity is the heterogeneity of cell fate that exists among pathogen-experienced lymphocytes. We show that a dividing T lymphocyte initially responding to a microbe exhibits unequal partitioning of proteins that mediate signaling, cell fate specification, and asymmetric cell division. Asymmetric segregation of determinants appears to be coordinated by prolonged interaction between the T cell and its antigen-presenting cell before division. Additionally, the first two daughter T cells displayed phenotypic and functional indicators of being differentially fated toward effector and memory lineages. These results suggest a mechanism by which a single lymphocyte can apportion diverse cell fates necessary for adaptive immunity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Chang, John T -- Palanivel, Vikram R -- Kinjyo, Ichiko -- Schambach, Felix -- Intlekofer, Andrew M -- Banerjee, Arnob -- Longworth, Sarah A -- Vinup, Kristine E -- Mrass, Paul -- Oliaro, Jane -- Killeen, Nigel -- Orange, Jordan S -- Russell, Sarah M -- Weninger, Wolfgang -- Reiner, Steven L -- AI007532/AI/NIAID NIH HHS/ -- AI042370/AI/NIAID NIH HHS/ -- AI053827/AI/NIAID NIH HHS/ -- AI055428/AI/NIAID NIH HHS/ -- AI061699/AI/NIAID NIH HHS/ -- AI069380/AI/NIAID NIH HHS/ -- CA114114/CA/NCI NIH HHS/ -- CA87812/CA/NCI NIH HHS/ -- DK007066/DK/NIDDK NIH HHS/ -- GM007170/GM/NIGMS NIH HHS/ -- R01 AI061699/AI/NIAID NIH HHS/ -- T32 AI055428/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 23;315(5819):1687-91. Epub 2007 Mar 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17332376" target="_blank"〉PubMed〈/a〉
    Keywords: Adoptive Transfer ; Animals ; Antigen Presentation ; Antigens, CD/analysis ; Antigens, CD8/analysis ; CD8-Positive T-Lymphocytes/*cytology/*immunology ; Cell Differentiation ; *Cell Division ; Cell Lineage ; Cell Polarity ; Dendritic Cells/immunology ; *Immunologic Memory ; Intracellular Signaling Peptides and Proteins/metabolism ; Listeria monocytogenes/immunology ; Listeriosis/immunology ; Lymphocyte Activation ; Membrane Proteins/analysis ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mitosis ; Nerve Tissue Proteins/analysis ; Protein Kinase C/metabolism ; Receptors, Antigen, T-Cell/immunology ; Receptors, Interferon/analysis ; Signal Transduction ; T-Lymphocyte Subsets/*cytology/*immunology ; T-Lymphocytes, Helper-Inducer/immunology
    Print ISSN: 0036-8075
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  • 79
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-01-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sapienza, Carmen -- New York, N.Y. -- Science. 2007 Jan 5;315(5808):46-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Fels Institute for Cancer Research and Department of Pathology, Temple University Medical School, 3307 North Broad Street, Philadelphia, PA 19140, USA. sapienza@temple.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17204629" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axonemal Dyneins ; Body Patterning ; Cell Line ; Cells, Cultured ; Chromatids/*physiology ; *Chromosome Segregation ; DNA Replication ; Dyneins/*genetics/*physiology ; Ectoderm/*cytology ; Embryonic Stem Cells/*cytology ; Endoderm/*cytology ; Interphase ; Mice ; Mitosis ; Recombination, Genetic ; Spindle Apparatus/physiology/ultrastructure
    Print ISSN: 0036-8075
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  • 80
    Publication Date: 2007-05-15
    Description: Hematopoietic stem cells in the bone marrow give rise to lymphoid progenitors, which subsequently differentiate into B and T lymphocytes. Here we show that the proto-oncogene LRF plays an essential role in the B versus T lymphoid cell-fate decision. We demonstrate that LRF is key for instructing early lymphoid progenitors in mice to develop into B lineage cells by repressing T cell-instructive signals produced by the cell-fate signal protein, Notch. We propose a new model for lymphoid lineage commitment, in which LRF acts as a master regulator of the cell's determination of B versus T lineage.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978506/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978506/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Maeda, Takahiro -- Merghoub, Taha -- Hobbs, Robin M -- Dong, Lin -- Maeda, Manami -- Zakrzewski, Johannes -- van den Brink, Marcel R M -- Zelent, Arthur -- Shigematsu, Hirokazu -- Akashi, Koichi -- Teruya-Feldstein, Julie -- Cattoretti, Giorgio -- Pandolfi, Pier Paolo -- CA-102142/CA/NCI NIH HHS/ -- R01 CA102142/CA/NCI NIH HHS/ -- R01 CA102142-06A1/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2007 May 11;316(5826):860-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17495164" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; B-Lymphocytes/*cytology/physiology ; Bone Marrow Cells/cytology ; Cell Lineage ; Cells, Cultured ; DNA-Binding Proteins/*genetics/physiology ; Gene Deletion ; Hematopoietic Stem Cells/*cytology/physiology ; *Lymphopoiesis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Biological ; *Proto-Oncogenes ; Receptors, Notch/*metabolism ; Signal Transduction ; T-Lymphocytes/*cytology/physiology ; Thymus Gland/cytology ; Transcription Factors/*genetics/physiology
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  • 81
    Publication Date: 2007-09-01
    Description: MicroRNAs (miRNAs) are evolutionarily conserved, 18- to 25-nucleotide, non-protein coding transcripts that posttranscriptionally regulate gene expression during development. miRNAs also occur in postmitotic cells, such as neurons in the mammalian central nervous system, but their function is less well characterized. We investigated the role of miRNAs in mammalian midbrain dopaminergic neurons (DNs). We identified a miRNA, miR-133b, that is specifically expressed in midbrain DNs and is deficient in midbrain tissue from patients with Parkinson's disease. miR-133b regulates the maturation and function of midbrain DNs within a negative feedback circuit that includes the paired-like homeodomain transcription factor Pitx3. We propose a role for this feedback circuit in the fine-tuning of dopaminergic behaviors such as locomotion.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782470/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782470/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jongpil -- Inoue, Keiichi -- Ishii, Jennifer -- Vanti, William B -- Voronov, Sergey V -- Murchison, Elizabeth -- Hannon, Gregory -- Abeliovich, Asa -- R01 NS064433/NS/NINDS NIH HHS/ -- R01 NS064433-01/NS/NINDS NIH HHS/ -- New York, N.Y. -- Science. 2007 Aug 31;317(5842):1220-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departments of Pathology and Neurology, Center for Neurobiology and Behavior, and Taub Institute, Columbia University, College of Physicians and Surgeons 15-403, 630 West 168th Street, New York, NY 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17761882" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/metabolism ; Aged ; Aged, 80 and over ; Animals ; Cell Differentiation ; Cell Line ; Cells, Cultured ; Dopamine/*metabolism ; Embryonic Stem Cells ; *Feedback, Physiological ; Female ; Gene Expression Regulation ; Homeodomain Proteins/*metabolism ; Humans ; Locomotion ; Male ; Mesencephalon/cytology/*metabolism ; Mice ; MicroRNAs/*metabolism ; Middle Aged ; Models, Biological ; Neurons/cytology/*metabolism ; Parkinson Disease/metabolism ; Rats ; Ribonuclease III/genetics/metabolism ; Transcription Factors/*metabolism ; Transcription, Genetic
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  • 82
    Publication Date: 2007-06-09
    Description: We describe a sensitive mRNA profiling technology, PMAGE (for "polony multiplex analysis of gene expression"), which detects messenger RNAs (mRNAs) as rare as one transcript per three cells. PMAGE incorporates an improved ligation-based method to sequence 14-nucleotide tags derived from individual mRNA molecules. One sequence tag from each mRNA molecule is amplified onto a separate 1-micrometer bead, denoted as a polymerase colony or polony, and about 5 million polonies are arrayed in a flow cell for parallel sequencing. Using PMAGE, we identified early transcriptional changes that preceded pathological manifestations of hypertrophic cardiomyopathy in mice carrying a disease-causing mutation. PMAGE provided a comprehensive profile of cardiac mRNAs, including low-abundance mRNAs encoding signaling molecules and transcription factors that are likely to participate in disease pathogenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jae Bum -- Porreca, Gregory J -- Song, Lei -- Greenway, Steven C -- Gorham, Joshua M -- Church, George M -- Seidman, Christine E -- Seidman, J G -- New York, N.Y. -- Science. 2007 Jun 8;316(5830):1481-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cardiovascular Division, Brigham and Women's Hospital, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17556586" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cardiomyopathy, Hypertrophic/*genetics/pathology/physiopathology ; DNA, Complementary ; Fibrosis/genetics/pathology ; Gene Expression Profiling/*methods ; *Gene Expression Regulation ; Gene Library ; Heart Ventricles/metabolism ; Mice ; Mutation ; Myocardial Contraction ; Myocardium/*metabolism ; Myosin Heavy Chains/genetics ; RNA, Messenger/genetics/metabolism ; Reproducibility of Results ; Sensitivity and Specificity ; Sequence Analysis, DNA ; Templates, Genetic ; Transcription Factors/genetics ; *Transcription, Genetic ; Ventricular Myosins/genetics
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  • 83
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    Unknown
    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-09-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hebert, Sebastien S -- De Strooper, Bart -- New York, N.Y. -- Science. 2007 Aug 31;317(5842):1179-80.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Human Genetics, VIB and KULeuven, Herestraat 49, Leuven, Belgium. bart.destrooper@med.kuleuven.be〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17761871" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/metabolism ; Animals ; Brain/physiology/*physiopathology ; Cell Death ; Cell Differentiation ; Cells, Cultured ; Dopamine/*metabolism ; Feedback, Physiological ; Humans ; Mice ; MicroRNAs/genetics/*metabolism ; Neurodegenerative Diseases/genetics/*physiopathology ; Neurons/cytology/metabolism/*physiology ; Parkinson Disease/genetics/*physiopathology ; RNA, Messenger/genetics/metabolism ; Ribonuclease III/metabolism ; Transcription Factors/metabolism
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  • 84
    Publication Date: 2007-08-04
    Description: Toll-like receptors (TLRs) trigger the production of inflammatory cytokines and shape adaptive and innate immunity to pathogens. We report the identification of B cell leukemia (Bcl)-3 as an essential negative regulator of TLR signaling. By blocking ubiquitination of p50, a member of the nuclear factor (NF)-kappaB family, Bcl-3 stabilizes a p50 complex that inhibits gene transcription. As a consequence, Bcl-3-deficient mice and cells were found to be hypersensitive to TLR activation and unable to control responses to lipopolysaccharides. Thus, p50 ubiquitination blockade by Bcl-3 limits the strength of TLR responses and maintains innate immune homeostasis. These findings indicate that the p50 ubiquitination pathway can be selectively targeted to control deleterious inflammatory diseases.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Carmody, Ruaidhri J -- Ruan, Qingguo -- Palmer, Scott -- Hilliard, Brendan -- Chen, Youhai H -- AI069289/AI/NIAID NIH HHS/ -- AI50059/AI/NIAID NIH HHS/ -- DK070691/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):675-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17673665" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cells, Cultured ; DNA/metabolism ; Female ; Half-Life ; Immune Tolerance ; Immunity, Innate ; Lipopolysaccharides/immunology ; Macrophage Activation ; Macrophages, Peritoneal/*immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; NF-kappa B p50 Subunit/*metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/genetics/*metabolism ; *Signal Transduction ; Toll-Like Receptors/*metabolism ; Transcription Factor RelA/metabolism ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic ; Tumor Necrosis Factor-alpha/genetics/metabolism ; Ubiquitin/metabolism
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  • 85
    Publication Date: 2007-08-19
    Description: Integral beta-barrel proteins are found in the outer membranes of mitochondria, chloroplasts, and Gram-negative bacteria. The machine that assembles these proteins contains an integral membrane protein, called YaeT in Escherichia coli, which has one or more polypeptide transport-associated (POTRA) domains. The crystal structure of a periplasmic fragment of YaeT reveals the POTRA domain fold and suggests a model for how POTRA domains can bind different peptide sequences, as required for a machine that handles numerous beta-barrel protein precursors. Analysis of POTRA domain deletions shows which are essential and provides a view of the spatial organization of this assembly machine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Seokhee -- Malinverni, Juliana C -- Sliz, Piotr -- Silhavy, Thomas J -- Harrison, Stephen C -- Kahne, Daniel -- GM34821/GM/NIGMS NIH HHS/ -- GM66174/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Aug 17;317(5840):961-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17702946" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Bacterial Outer Membrane Proteins/*chemistry/genetics/*metabolism ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Dimerization ; Escherichia coli/*chemistry/*metabolism ; Escherichia coli Proteins/*chemistry/genetics/*metabolism ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Lipoproteins/chemistry/metabolism ; Models, Biological ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Binding ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Protein Transport
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  • 86
    Publication Date: 2007-08-04
    Description: The cellular immune response to tissue damage and infection requires the recruitment of blood leukocytes. This process is mediated through a classical multistep mechanism, which involves transient rolling on the endothelium and recognition of inflammation followed by extravasation. We have shown, by direct examination of blood monocyte functions in vivo, that a subset of monocytes patrols healthy tissues through long-range crawling on the resting endothelium. This patrolling behavior depended on the integrin LFA-1 and the chemokine receptor CX(3)CR1 and was required for rapid tissue invasion at the site of an infection by this "resident" monocyte population, which initiated an early immune response and differentiated into macrophages.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Auffray, Cedric -- Fogg, Darin -- Garfa, Meriem -- Elain, Gaelle -- Join-Lambert, Olivier -- Kayal, Samer -- Sarnacki, Sabine -- Cumano, Ana -- Lauvau, Gregoire -- Geissmann, Frederic -- G0900867/Medical Research Council/United Kingdom -- New York, N.Y. -- Science. 2007 Aug 3;317(5838):666-70.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Nationale de la Sante et de la Recherche Medicale (INSERM) U838, Laboratory of Biology of the Mononuclear Phagocyte System, and Cellular and Molecular imaging core facility, Institut Federatif de Recherche Necker-Enfants Malades, Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17673663" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Vessels/*immunology ; Cell Adhesion ; Cell Differentiation ; Cell Movement ; Dermis/immunology ; Endothelium, Vascular/*immunology ; Gene Expression Regulation ; Immunity, Innate ; Inflammation/*immunology ; Listeria monocytogenes ; Listeriosis/immunology ; Lymphocyte Function-Associated Antigen-1/physiology ; Macrophages/cytology/immunology ; Mesenteric Arteries/immunology ; Mesenteric Veins/immunology ; Mice ; Microscopy, Confocal ; Monocytes/cytology/*immunology/physiology ; Receptors, Chemokine/analysis/physiology
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  • 87
    Publication Date: 2007-11-17
    Description: CD4+ T helper 1 (TH1) cells are important mediators of inflammation and are regulated by numerous pathways, including the negative immune receptor Tim-3. We found that Tim-3 is constitutively expressed on cells of the innate immune system in both mice and humans, and that it can synergize with Toll-like receptors. Moreover, an antibody agonist of Tim-3 acted as an adjuvant during induced immune responses, and Tim-3 ligation induced distinct signaling events in T cells and dendritic cells; the latter finding could explain the apparent divergent functions of Tim-3 in these cell types. Thus, by virtue of differential expression on innate versus adaptive immune cells, Tim-3 can either promote or terminate TH1 immunity and may be able to influence a range of inflammatory conditions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Anderson, Ana C -- Anderson, David E -- Bregoli, Lisa -- Hastings, William D -- Kassam, Nasim -- Lei, Charles -- Chandwaskar, Rucha -- Karman, Jozsef -- Su, Ee W -- Hirashima, Mitsuomi -- Bruce, Jeffrey N -- Kane, Lawrence P -- Kuchroo, Vijay K -- Hafler, David A -- R01 AI067544/AI/NIAID NIH HHS/ -- R01 AI067544-01A2/AI/NIAID NIH HHS/ -- R56 AI067544/AI/NIAID NIH HHS/ -- R56 AI067544-01A1/AI/NIAID NIH HHS/ -- R56 AI067544-02/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2007 Nov 16;318(5853):1141-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18006747" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD11b/immunology ; Astrocytes/immunology ; Central Nervous System Neoplasms/immunology ; Dendritic Cells/immunology ; Encephalomyelitis, Autoimmune, Experimental/immunology ; Galectins/immunology ; Glioblastoma/immunology ; Humans ; Immunity, Innate ; Inflammation Mediators/*immunology ; Lipopolysaccharides/immunology ; Macrophages/immunology ; Membrane Proteins/biosynthesis/*immunology ; Mice ; Microglia/immunology ; Multiple Sclerosis/immunology ; Rats ; Receptors, Immunologic/biosynthesis/*immunology ; Receptors, Virus/biosynthesis/*immunology ; Signal Transduction ; T-Lymphocytes/immunology ; Th1 Cells/*immunology ; Toll-Like Receptors
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  • 88
    Publication Date: 2007-10-13
    Description: Jacobs et al. (Reports, 23 March 2007, p. 1723) reported that plasticity in the mammalian visual system permitted the emergence of "a new dimension of sensory experience" in mice genetically engineered to express a human long-wavelength-sensitive cone photopigment. However, neither neural plasticity nor a new dimension of sensory experience is required to explain their results.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Makous, Walter -- New York, N.Y. -- Science. 2007 Oct 12;318(5848):196; author reply 196.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Visual Science, University of Rochester, Rochester, NY 14627, USA. walt@cvs.rochester.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17932271" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Color Perception/genetics ; Genetic Engineering ; Humans ; Light ; Mice ; *Neuronal Plasticity ; Retinal Cone Photoreceptor Cells/*physiology ; Retinal Pigments/*genetics/*physiology
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  • 89
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-04-21
    Description: Animal germ cells differentiate as sperm or eggs, depending on their sex. Somatic signals tell germ cells whether they reside in a male or female body, but how do germ cells interpret those external cues to acquire their own sexual identity? A critical aspect of a germ cell's sexual puzzle is that the sperm/egg decision is closely linked to the cell-cycle decision between mitosis and meiosis. Molecular studies have begun to tease apart the regulators of both decisions, an essential step toward understanding the regulatory logic of this fundamental question of germ cell biology.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kimble, Judith -- Page, David C -- New York, N.Y. -- Science. 2007 Apr 20;316(5823):400-1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706, USA. jekimble@wisc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17446389" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Lineage ; Female ; Germ Cells/*cytology/physiology ; Male ; *Meiosis ; *Mitosis ; Models, Biological ; Oogenesis ; Ovum/cytology ; Spermatogenesis ; Spermatozoa/cytology
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  • 90
    Publication Date: 2007-04-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2007 Apr 13;316(5822):182.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17431141" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Culture Techniques ; *Embryonic Stem Cells ; Humans ; *Intellectual Property ; Mice ; *Patents as Topic/legislation & jurisprudence ; Primates ; Wisconsin
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  • 91
    Publication Date: 2007-03-31
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Andrews, Katherine T -- Gatton, Michelle L -- Skinner-Adams, Tina S -- McCarthy, James S -- Gardiner, Donald L -- New York, N.Y. -- Science. 2007 Mar 30;315(5820):1791; author reply 1791.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17395812" target="_blank"〉PubMed〈/a〉
    Keywords: Africa South of the Sahara/epidemiology ; Animals ; Antimalarials/*pharmacology/therapeutic use ; HIV/*drug effects ; HIV Infections/*complications/drug therapy/epidemiology ; HIV Protease Inhibitors/*pharmacology/therapeutic use ; Humans ; Malaria, Falciparum/*complications/drug therapy/epidemiology ; Models, Biological ; Plasmodium falciparum/*drug effects ; Prevalence ; Viral Load ; Virus Replication/drug effects
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  • 92
    Publication Date: 2007-03-03
    Description: Coronary artery disease (CAD) is the leading cause of death worldwide and is commonly caused by a constellation of risk factors called the metabolic syndrome. We characterized a family with autosomal dominant early CAD, features of the metabolic syndrome (hyperlipidemia, hypertension, and diabetes), and osteoporosis. These traits showed genetic linkage to a short segment of chromosome 12p, in which we identified a missense mutation in LRP6, which encodes a co-receptor in the Wnt signaling pathway. The mutation, which substitutes cysteine for arginine at a highly conserved residue of an epidermal growth factor-like domain, impairs Wnt signaling in vitro. These results link a single gene defect in Wnt signaling to CAD and multiple cardiovascular risk factors.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945222/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2945222/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mani, Arya -- Radhakrishnan, Jayaram -- Wang, He -- Mani, Alaleh -- Mani, Mohammad-Ali -- Nelson-Williams, Carol -- Carew, Khary S -- Mane, Shrikant -- Najmabadi, Hossein -- Wu, Dan -- Lifton, Richard P -- K08 HD041481/HD/NICHD NIH HHS/ -- K08 HD041481-01/HD/NICHD NIH HHS/ -- P01DK68229/DK/NIDDK NIH HHS/ -- P50 HL55007/HL/NHLBI NIH HHS/ -- R01 AR051476/AR/NIAMS NIH HHS/ -- R01 AR051476-01A1/AR/NIAMS NIH HHS/ -- R01 AR051476-02/AR/NIAMS NIH HHS/ -- R01 AR051476-03/AR/NIAMS NIH HHS/ -- R01 AR051476-04/AR/NIAMS NIH HHS/ -- New York, N.Y. -- Science. 2007 Mar 2;315(5816):1278-82.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Internal Medicine, Howard Hughes Medical Institute and Yale University School of Medicine, New Haven, CT 06510, USA. arya.mani@yale.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17332414" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; Aged ; Aged, 80 and over ; Amino Acid Substitution ; Animals ; Chromosomes, Human, Pair 12/genetics ; Coronary Disease/*genetics/metabolism ; Family Health ; Female ; Genetic Linkage ; *Genetic Predisposition to Disease ; Humans ; LDL-Receptor Related Proteins/*genetics/physiology ; Lipids/blood ; Low Density Lipoprotein Receptor-Related Protein-6 ; Male ; Metabolic Syndrome X/*genetics/metabolism ; Mice ; Middle Aged ; *Mutation, Missense ; NIH 3T3 Cells ; Osteoporosis/genetics ; Pedigree ; Risk Factors ; Signal Transduction ; Wnt Proteins/metabolism
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  • 93
    Publication Date: 2007-10-06
    Description: Telomeres, the DNA-protein complexes located at the end of linear eukaryotic chromosomes, are essential for chromosome stability. Until now, telomeres have been considered to be transcriptionally silent. We demonstrate that mammalian telomeres are transcribed into telomeric repeat-containing RNA (TERRA). TERRA molecules are heterogeneous in length, are transcribed from several subtelomeric loci toward chromosome ends, and localize to telomeres. We also show that suppressors with morphogenetic defects in genitalia (SMG) proteins, which are effectors of nonsense-mediated messenger RNA decay, are enriched at telomeres in vivo, negatively regulate TERRA association with chromatin, and protect chromosome ends from telomere loss. Thus, telomeres are actively transcribed into TERRA, and SMG factors represent a molecular link between TERRA regulation and the maintenance of telomere integrity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Azzalin, Claus M -- Reichenbach, Patrick -- Khoriauli, Lela -- Giulotto, Elena -- Lingner, Joachim -- New York, N.Y. -- Science. 2007 Nov 2;318(5851):798-801. Epub 2007 Oct 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Swiss Institute for Experimental Cancer Research (ISREC), CH-1066 Epalinges, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17916692" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Blotting, Northern ; Cells, Cultured ; Chromosomes, Human ; Chromosomes, Mammalian ; HeLa Cells ; Humans ; In Situ Hybridization, Fluorescence ; Mice ; Molecular Sequence Data ; Proteins/metabolism ; RNA/*genetics ; Repetitive Sequences, Nucleic Acid ; Telomerase/physiology ; Telomere/*genetics ; Transcription, Genetic ; Tumor Cells, Cultured
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  • 94
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-02-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Holden, Constance -- New York, N.Y. -- Science. 2007 Feb 9;315(5813):760-1.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17289957" target="_blank"〉PubMed〈/a〉
    Keywords: Adult Stem Cells/*cytology/transplantation ; Animals ; Bone Marrow Cells/*cytology ; Bone Marrow Transplantation ; Cell Culture Techniques ; Cell Differentiation ; Cell Fusion ; Embryonic Stem Cells/cytology ; Hematopoiesis ; Humans ; Mice ; Multipotent Stem Cells/*cytology/transplantation ; Pluripotent Stem Cells/cytology ; Stromal Cells/*cytology/transplantation
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  • 95
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2007-03-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, Jean -- New York, N.Y. -- Science. 2007 Mar 2;315(5816):1211-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/17332387" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antineoplastic Agents/metabolism/*therapeutic use ; Apoptosis ; Clinical Trials as Topic ; Drug Screening Assays, Antitumor ; *Genes, p53 ; Genetic Engineering ; Humans ; Imidazolines/therapeutic use ; Mice ; Mutation ; Neoplasm Transplantation ; Neoplasms/*drug therapy/genetics/metabolism/pathology ; Proto-Oncogene Proteins c-mdm2/metabolism ; Pyrimidines/metabolism/therapeutic use ; Tumor Suppressor Protein p53/*metabolism
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  • 96
    Publication Date: 2007
    Description: Animals and fungi assemble a contractile ring of actin filaments and the motor protein myosin to separate into individual daughter cells during cytokinesis. We used fluorescence microscopy of live fission yeast cells to observe that membrane-bound nodes containing myosin were broadly distributed around the cell equator and assembled into a contractile ring through stochastic motions, after a meshwork of dynamic actin filaments appeared. Analysis of node motions and numerical simulations supported a mechanism whereby transient connections are established when myosins in one node capture and exert force on actin filaments growing from other nodes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vavylonis, Dimitrios -- Wu, Jian-Qiu -- Hao, Steven -- O'Shaughnessy, Ben -- Pollard, Thomas D -- GM-26132/GM/NIGMS NIH HHS/ -- GM-26338/GM/NIGMS NIH HHS/ -- R01 GM026132/GM/NIGMS NIH HHS/ -- R01 GM026338/GM/NIGMS NIH HHS/ -- R01 GM086546/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2008 Jan 4;319(5859):97-100. Epub 2007 Dec 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemical Engineering, Columbia University, New York, NY 10027, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18079366" target="_blank"〉PubMed〈/a〉
    Keywords: Actin Cytoskeleton/*metabolism/ultrastructure ; *Cytokinesis ; Microscopy, Confocal ; Microscopy, Fluorescence ; Models, Biological ; Monte Carlo Method ; Movement ; Myosin Type II/*metabolism ; Schizosaccharomyces/*cytology/*metabolism/ultrastructure ; Stochastic Processes
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  • 97
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2005-10-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marx, Jean -- New York, N.Y. -- Science. 2005 Oct 7;310(5745):43-5.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16210515" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Autophagy ; Brain-Derived Neurotrophic Factor/metabolism ; Cells, Cultured ; Clinical Trials as Topic ; Corpus Striatum/pathology ; Disease Models, Animal ; Gene Expression Regulation ; Humans ; Huntington Disease/*drug therapy/genetics/pathology/*physiopathology ; Mice ; Mitochondria/metabolism ; Mutation ; Nerve Tissue Proteins/chemistry/*genetics/metabolism/*physiology ; Neurons/*physiology ; Nuclear Proteins/chemistry/*genetics/metabolism/*physiology ; Peptides ; Transcription Factors/metabolism ; Trinucleotide Repeat Expansion
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  • 98
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2005-09-06
    Description: Large numbers of noncoding RNA transcripts (ncRNAs) are being revealed by complementary DNA cloning and genome tiling array studies in animals. The big and as yet largely unanswered question is whether these transcripts are relevant. A paper by Willingham et al. shows the way forward by developing a strategy for large-scale functional screening of ncRNAs, involving small interfering RNA knockdowns in cell-based screens, which identified a previously unidentified ncRNA repressor of the transcription factor NFAT. It appears likely that ncRNAs constitute a critical hidden layer of gene regulation in complex organisms, the understanding of which requires new approaches in functional genomics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mattick, John S -- New York, N.Y. -- Science. 2005 Sep 2;309(5740):1527-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Australian Research Council Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia. j.mattick@imb.uq.edu.au〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16141063" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Base Sequence ; Conserved Sequence ; DNA-Binding Proteins/antagonists & inhibitors ; *Genomics ; Humans ; Mice ; NFATC Transcription Factors ; Nuclear Proteins/antagonists & inhibitors ; *RNA Interference ; RNA, Untranslated/antagonists & inhibitors/genetics/*physiology ; Transcription Factors/antagonists & inhibitors ; beta Karyopherins/metabolism
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  • 99
    Publication Date: 2005-01-22
    Description: Territorial behavior is expected to buffer populations against short-term environmental perturbations, but we have found that group living in African lions causes a complex response to long-term ecological change. Despite numerous gradual changes in prey availability and vegetative cover, regional populations of Serengeti lions remained stable for 10- to 20-year periods and only shifted to new equilibria in sudden leaps. Although gradually improving environmental conditions provided sufficient resources to permit the subdivision of preexisting territories, regional lion populations did not expand until short-term conditions supplied enough prey to generate large cohorts of surviving young. The results of a simulation model show that the observed pattern of "saltatory equilibria" results from the lions' grouping behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Packer, Craig -- Hilborn, Ray -- Mosser, Anna -- Kissui, Bernard -- Borner, Markus -- Hopcraft, Grant -- Wilmshurst, John -- Mduma, Simon -- Sinclair, Anthony R E -- New York, N.Y. -- Science. 2005 Jan 21;307(5708):390-3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology, Evolution, and Behavior, University of Minnesota, 1987 Upper Buford Circle, Saint Paul, MN 55108, USA. packer@cbs.umn.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/15662005" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; Antelopes ; *Behavior, Animal ; *Ecosystem ; Environment ; Female ; *Lions/physiology ; Male ; Models, Biological ; Plants ; Population Density ; Population Dynamics ; Predatory Behavior ; Reproduction ; Seasons ; Social Behavior ; Stochastic Processes ; Tanzania ; *Territoriality
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 100
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2005-07-16
    Description: Many biological membranes adapt in response to environmental conditions. We investigated how the composition and architecture of photosynthetic membranes of a bacterium change in response to light, using atomic force microscopy. Despite large modifications in the membrane composition, the local environment of core complexes remained unaltered, whereas specialized paracrystalline light-harvesting antenna domains grew under low-light conditions. Thus, the protein mixture in the membrane shows eutectic behavior and can be mimicked by a simple model. Such structural adaptation ensures efficient photon capture under low-light conditions and prevents photodamage under high-light conditions.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Scheuring, Simon -- Sturgis, James N -- New York, N.Y. -- Science. 2005 Jul 15;309(5733):484-7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institut Curie, Unite Mixte de Recherche-CNRS 168, 11 rue Pierre et Marie Curie, 75231 Paris Cedex 05, France. simon.scheuring@curie.fr〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16020739" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Biological ; Bacterial Chromatophores/*chemistry/*ultrastructure ; Bacteriochlorophylls/analysis ; Computer Simulation ; Crystallization ; *Light ; Light-Harvesting Protein Complexes/analysis/*chemistry ; Microscopy, Atomic Force ; Models, Biological ; Monte Carlo Method ; *Photosynthesis ; Protein Subunits/analysis ; Rhodospirillum/chemistry/growth & development/*physiology/*ultrastructure
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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